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180 Cards in this Set
- Front
- Back
what are the 21-hydroxy-corticosteroids?
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deoxycorticosterone and aldosterone
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what is the physiologic mineralcorticoid in humans?
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aldosterone
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a pathway that goes from pregnenolone through progesterone synthesizes what? where does this pathway reside?
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synthesizes mineralocorticoids deoxycorticosterone and aldosterone and resides in the outer layer (zona glomerulosa) of the adrenal cortex
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a pathway going through 17-hydroxyprogesterone synthesizes what? where is this pathway?
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cortisol; pathway is in the middle layer of the adrenal cortex (zona fasciculata)
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what is a 17-hydroxy-corticosteroid?
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cortisol
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pathway in which a 2C side chain is cleaved from the 17-hydroxysteroid precursors synthesizes what?
where does this pathway take place? |
1. the adrenal androgens dehydroepandrosterone and androstenedione
2. inner layer of adrenal cortex (zona reticularis) |
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what are the 17-ketosteroids?
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adrenal androgens
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steroid hormones are transported in the what?
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plasma bound to plasma proteins
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The following steroid hormones are transported in the plasma bound to what plasma proteins:
1. Cortisol and progesterone? 2. Aldosterone? 3. Dehydroepiandrosterone and androstenedione? |
1. corticosteroid-binding globulin (CBG) also called transcortin; small proportion of cortisol is bound to serum albumin
2. albumin mostly, small portion to transcortin 3. mostly albumin |
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amount of transcortin in plasma is elevated and lowered by what?
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elevated by female sex hormones (estrogens) and lowered by liver disease, amyloid disease of multiple myelome
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what % of the steroid hormones are unbound (free)?
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about 10%
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where are steroid hormones converted to inactive metabolites?
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peripheral tissues and by the liver
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how are steroid hormones gotten rid of?
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- they are converted to inactive tetrahydro-derivatives
- they are conjugated to glucuronic or sulfuric acids and excreted in the urine |
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the secretion of adrenocortical hormones is controlled by the what?
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anterior pituitary, kidney, and plasma electrolytes
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cortical secretion is regulated by what system?
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hypothalamic-pituitary-adrenal system
a. hypothalamus secretes CRH in response to variety of stimuli, including fall in plasma cortisol b. CRH travels via a hypothalamic-pituitary portal circulation to anterior pituitary where it stimulates secretion of ACTH c. ACTH travels via bloodstream to adrenal cortex where it stimulates rate-limiting step in steroid hormone synthesis: conversion of cholesterol to pregnenolone, increasing synthesis and secretion of adrenal corticosteroids d. cortisol feeds back on hypothalamus to reduce CRF secretion e. ACTH secretion undergoes diurnal (daily) variation, peaking in late sleep |
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when does ACTH peak?
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late sleep
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what system regulates secretion of aldosterone?
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renin-angiotensin system
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control of adrenal androgen secretion
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not clear, but their secretion rises at puberty
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what are the steps in the renin-angiotensin system for regulating aldosterone secretion?
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1. when volume or pressure of blood perfusing the kidney falls, juxtaglomerular cells secrete a proteolytic enzyme rein into blood stream
2. renin cleaves angiotensinogen, protein from liver, to form angiotensin I, a decapeptide 3. angiotensin I is cleaved by angiotensin converting enzyme (ACE), a peptidase, to angiotensin II, an octapeptide hormone 4. angiotensin II raises blood pressure and stimulates secretion of aldosterone by adrenal zona glomerulosa cells |
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what are the diseases of the adrenal cortex ?
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1. hormone deficiency: primary adrenal cortical insufficiency (addison's disease) - failure of adrenal cortex to secrete sufficient cortisol
2. cortisol excess: cushing's syndrome 3. aldosterone excess: primary aldosteronism (conn's syndrome) - due to an adenoma in zona glomerulosa |
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what are the clinical features of addison's disease (primary adrenal cortical insufficiency)?
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1. hypoglycemia w/ extreme sensitivity to insulin
2. intoelrance to stress 3. anorexia, weight loss, nausea, severe weakness 4. low blood pressure 5. decreased glomerular filtration rate w/ impaired ability to excrete a water load 6. low blood Na+, high K+. history of craving salt 7. hyperpigmentation of the skin and mucous membranes due to high levels of ACTH and associated products of the POMC gene |
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treatment for addison's disease
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replacing glucocorticoids, and mineralcorticoids if necessary
|
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how does cortisol become present in excess?
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- through independent, autonomous secretion of cortisol by an adrenal adenoma or carcinoma
- increased production of ACTH by a pituitary adenoma (cushing's disease) leading to elevated cortisol secretion by the adrenal - ectopic ACTH or CRH production by a tumor outside the pituitary - high dose administration of synthetic corticosteroids [iatrogenic (induced) cushing's syndrome] |
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clinical features of cushing's syndrome
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1. weight gain (corticosteroid induced lipogenesis), principally around abdomen
2. proximal muscle weakness (corticosteroid myopathy) leading to thin arms and legs 3. moonface appearance 4. thin easily bruised skin w/ purple stria on the lower abdomen, upper arms and thighs due to catabolic effects of corticosteroids 5. back pain due to corticosteroid-induced osteoporosis 6. excessive hair growth and amenorrhea (absence of cycle) in women due to elevated adrenal androgens 7. hyperglycemia due to corticosteroid-induced gluconeogenesis 8. hypertension due to Na+ retention 9. increased susceptibility to infection due to immunosuppression 10. increased CNS activity |
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clinical features of conn's syndrome (primary aldosteronism)
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1. hypertension due to Na+ and H2O retention
2. kidney excretes K+ and H+ in place of Na+ leading to depressed blood K+ (hypokalemia) and H+ (alkalosis) 3. muscle weakness due to hypokalemia |
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treatment of pituitary aldosteronism
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usually by surgical removal of adenoma-carrying adrenal gland. medical treatment w/ spironolactone, an aldosterone antagonist can be used in patients who are unsuitable for surgery
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what hormones regulate the reproductive systems?
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sex hormones
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male reproductive system consists of the organs that provide for the production and delivery of what?
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live, motile sperm
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primary male sex organ
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seminiferous tubules of testis - site of sperm production
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male accessory sex organs
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prostate and seminal vesicles - provide for maturation of sperm and keep them alive
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secondary male sex organs
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1. scrotum - maintains sperm at lower temp.
2. penis - delivers sperm |
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testosterone is synthesized and secreted by what?
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interstitial cells of leydig in the testis
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male sex hormone
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testosterone
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how is testosterone produced in interstitial cells of leydig?
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1. pathway begins w/ cholesterole and follows the same reactions to androstenedione as found in adrenal cortex
2. interstitial cells reduce androstenedione to testosterone 3. some tissues convert testosterone to dihydrotestosterone, for these tissues testosterone is a prohormone |
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some tissues convert testosterone to what?
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dihydrotestosterone, for these tissues testosterone is a prohormone
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how does testosterone travel in the blood?
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bound to proteins:
1. sex hormone binding globulin (SHBG) 2. serum albumin |
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what are the roles of testosterone that are not obviously related to reproduction?
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1. is anabolic: stimulates protein synthesis, particularly in skeletal muscle. responsible for spurt in linear growth and increase in m. mass during puberty
2. promotes skin maturation and increased sebaceous gland activity 3. affects hair distribution - lateral front region of scalp, male pattern baldness - axilla, low pubic region, and lower part of limbs develop hair @ puberty in both sexes - hair growth on face, ears, nasal tip and upper pubic triangle require adult male levels of testosterone 4. promotes voice deepening 5. associated w/ aggressive personality |
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reproductive actions of testosterone
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1. promotes spermatogenesis, this also requires FSH from anterior pituitary
2. promotes maturation and maintains the function of sex-accessory organs: prostate and seminal vesicles. 3. promotes increase in size and pigmentation of the male secondary sex organs 4. increases male sexual activity: frequency of erections |
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what do secretions from the prostate and seminal vesicles promote?
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sperm maturation and viability
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what is a major difference between testosterone and other steroid hormones?
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in some target tissues testosterone is converted to dihydrotestosterone, which is the active chemical messenger in those tissues
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testosterone acts by the mechanism common to all steroid hormones which is altering what?
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gene expression in target tissues
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testicular function is regulated by what?
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pituitary gonadotrophins, LH, and FSH
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how does FSH act on the testis and how is its action controlled?
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FSH stimulates spermatogenesis in the seminiferous tubules of the testis. Its control is not well understood. It may depend on inhibin, a protein from the seminiferous tubules, and on the females sex hormone estradiol secreted by the leydig cells
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what type of effect does testosterone have on the hypothalamus?
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it exerts feedback control on the hypothalamic secretion of gonadotropin releasing hormone (GnRH) which regulates pituitary secretion of LH
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what affect does LH have on testicular function?
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- stimulates testosterone synthesis and secretion by the interstitial cells of the testis (leydig cells)
- increases conversion of cholesterol to pregnenolone and subsequent intermediates in steroid hormone biosynthetic pathway - LH is mediated by cAMP |
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LH is mediated by what?
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cAMP
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how is testosterone inactivated?
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by oxidation of alcohol @ position 17, yielding 2 ketosteroids. occurs in peripheral tissues and lvier. 17-ketosteroids are excreted in the urine as their sulfates and glucosiduronates
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what does the female reproductive system include?
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ovaries, uterus, and mammary glands
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reproduction in female mammal requires that what 6 events occur in proper sequence?
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1. ovulation - release of mature ovum from ovarian follicle
2. fertilization - of ovum by sperm while ovum is in fallopian tube 3. implantation - of fertilized ovum in properly prepared uterine endometrium 4. gestation - carrying developing fetus in uterus until time of birth 5. parturition - delivery of living infant through cervix and vagina to outside world 6. lactation - formation and release of milk to noursn growing infant |
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reproduction in females is regulated by female sex hormones secreted by what?
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ovary, placent, and anterior pituitary
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what hormones does the ovary secrete?
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2 steroid female sex hormones - estradiol (an estrogen) and progesterone, and a protein hormone, relaxin
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what hormones does the placenta secrete?
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estrogens, progesterone, relaxin, and 3 counterparts of pituitary hormones:
1. human chorionic gonadotropin (HCG) w/ LH-like activity 2. human placental lactogen (HPL) w/ prolactin-like activity 3. human chorionic thyrotropin (HCT) w/ TSH-like activity |
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what reproductive hormones does the pituitary secrete?
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1. gonadotropins - FSH and LH which regulate the ovary
2. prolactin - stimulates milk production by mammary gland |
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what is the most active natural estrogen?
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estradiol
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estriol is synthesized and secreted in large amounts by the what?
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fetoplacental unit during pregnancy
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what are the hormones of the woman?
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estrogens
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what are the general actions of estrogens?
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1. stimulation of bone calcification in general and epiphyseal closure in long bones
2. accumulation of subcutaneous fat in feminine contour 3. maturation of skin |
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reproduction actions of estradiol
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1. maturation of the organs of the female reproductive tract. the uterus, cervix and vagina assume their adult size and capability
2. proliferation of vaginal epithelium 3. secretion of watery mucous by cervical glands 4. proliferation of uterine endometrium 5. duct proliferation and fat deposition in mammary gland |
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progesterone exerts its reproductive actions on what type of tissues?
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tissues that have been prepared by estrogens
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what does progesterone do?
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1. transforms proliferative uterine endometrium into a secretory endometrium suitable for implantation of fertilized ovum
2. prevents synchronized contraction of uterine m. 3. maintains pregnancy (progesterone for gestation) 4. stimulates growth of lobulo-alveolar system in mammary gland |
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FSH and LH control what?
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secretion of estradiol and progesterone by the ovary from anterior pituitary, growth of ovarian follicle, ovulation, and luteinization
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what stimulates secretion of FSH and LH?
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GnRH stimulates secretion of FSH and LH. hypothalamus secretes GnRH in a cyclic pattern of about 28 days
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how is gonadotropin releasing hormone secreted?
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by hypothalamus in a cyclic pattern of about 28 days
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what prevents breakdown of corpus luteum and maintains progesterone secretion after implantation?
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HCG secreted from chorion cells
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progesterone is synthesized from what?
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cholesterol by the same reactions as in the adrenal cortex
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estrogens are synthesized by what?
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aromatization of androgens
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adrenal androgens may be aromatized in what tissues?
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peripheral tissues, particularly adipose tissue. accounts for estrogenization of postmenopausal women and patients w/ liver cirrhosis
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do the testis and adrenal cortex secrete estradiol?
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small amounts
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what carries out the conversion of estrogens from androgens?
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aromatase (P450arom), the enzyme complex that carries out this conversion is abundant in the endoplasmic reticulum of the ovarian follicle, corpus luteum, and placenta
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how are estrogens transported in the blood?
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bound to sex hormone binding globulin (SHBG) and serum albumin.
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how is progesterone transported ?
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bound to corticosteroid binding globulin (CBG)
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estrogens and progesterones are metabolized to what?
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inactive products and excreted as their glucosiduronates or sulfates
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hypothalamic-anterior pituitary endocrine axis provides a link between what?
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CNS and endocrine system
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human pituitary is located where? is an extension of what?
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at the base of the brain just behind the optic chiasm, is an extension of the hypothalamus
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what are the 2 lobes of the pituitary and what does each secrete?
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1. neurohypophysis or posterior pituitary, secretes 2 peptide hormones - oxytocin and vasopressin
2. adenohypophysis or anterior pituitary, secretes a variety of protein and glycoprotein hormones |
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are the hypothalamus and pituitary similar?
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there is a close anatomic and functional relationship between them
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describe the portal circulation between the hypothalamus and pituitary
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1. blood enters this system via the superior hypophyseal a. this a. branches into a primary capillary plexus in the median eminence
2. primary capillary plexus drains into the hypophyseal portal vessels which travels down the stalk to the anterior pituitary where they form the anterior pituitary sinusoids 3. anterior pituitary sinusoids empty into hypophyseal v. 4. blood from hypophyseal v. passes into general circulation |
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what parts of the brain is the hypothalamus connected to?
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all or nearly all parts; has many interconnections w/ rest of CNS
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nerve impulses arring at the hypothalamus can do what?
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trigger neurosecretory cells to secrete releasing hormones
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describe how neurosecretory cells are stimulated, what they resemble, and how they act/
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- resemble other nerve cells morphologically
- stimulated by neurotransmitters such as acetylcholine, norepinephrine, serotonin, and dopamine - differ from ordinary n. cells in the way they act - instead of releasing neurotransmitters to depolarize another neuron or cell, they secrete releasing hormones (peptides) |
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what are hypothalamic releasing hormones? what do they control?
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they are polypeptides that control the release of hormones by the anterior pituitary
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describe how the hypothalamic releasing hormoens often exist in pairs
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one stimulates and the other inhibits the release of pituitary hormone
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how strong are the releasing hormones of the hypothalamus?
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extremely potent - 10 ng of releasing hormone will liberate 1 mg of pituitary hormone
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how do the hypothalamus, pituitary, target glands, and CNS influence each other?
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through feedback loops
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short loop feedback in network between hypothalamus, pituitary glands, target glands, and CNS
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refers to effect of pituitary hormones on hypothalamus
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long loop feedback in network between hypothalamus, pituitary glands, target glands, and CNS
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refers to effect of end organ hormones on hypothalamus
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most of the pituitary hormones stimulate what?
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another endocrine gland - the target gland - to secrete its hormone
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1. low levels of target gland hormone usually stimulate what?
2. high levels of target gland hormone usually what? |
1. secretion of a releasing hormone
2. inhibit secretion of releasing hormone |
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describe what the set pt. for each system is?
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pt. at which the level of circulating target gland hormone is maintained. can be changed by CNS stimuli, levels of other hormones, and changes in circulating metabolites
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do end organ hormones affect the hypothalamus or pituitary?
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may affect both
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major site for feedback control by thyroid hormones is on the what?
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pituitary rather than hypothalamus
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1. what is the target gland of growth hormone?
2. how is it regulated? |
1. exception in that it has no specific target gland, but acts on a variety of metabolic processes throughout body
2. regulated by substrates for pathways it controls, such as certain AAs or by metabolic end products wuch as glucose or FAs |
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1. in addition to feedback regulation, CNS signals influence the ________ of releasing factors
2. how? |
1. secretion
2. exteroreceptive organs such as - ears, eyes, nose, and skin, interoreceptive sensors, and cerebral cortex all send neural signals to hypothalamic neurosecretory cells either directly or through relays in brain. these signals may be excitatory or inhibitory |
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in relation to the light-dark, sleep-waking cycle, what are some of the rhythms the hypothalamic-pituitary-target organ systems respond to?
|
1. many are circadian (bout 24 hr) rhythms
2. some are ultradian (90-120 minutes) rhythms 3. a few are infradian (monthly) |
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1. pituitary output of tropic hormone does what?
2. hypothalamus acts as a computer that adjusts to what? |
1. raises the output of target gland hormone to a certain level which then feeds back to lower the output of tropic hormone
2. suit changing needs such as changes in environmental temp., emotional shifts, growth, development, sleeping, and waking |
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hormones secreted by anterior pituitary fall into what 2 groups?
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1. tropic hormones - maintain target glands and stimulate production of target gland hormones
2. growth hormone and prolactin - acts more generally, their target tissues include organds that are not endocrine glands |
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thyroid stimulating hormone (TSH, thyrotropin) stimulates what?
|
growth of thyroid gland and secretion of thyroid hormones
|
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describe the structure of TSH
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glycoprotein of about 30, 000 kDA, consists of 1 alpha and 1 beta subunit
|
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T or F FSH and LH are 2 subunit glycoproteins
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T
|
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compare the alpha and beta subunits of TSH, FSH, and LH
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the alpha subunits are common to all 3 of these tropic hormones; beta-subunits are different in each of the 3 and confer hormonal specificity
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if the alpha and beta subunits of FSH, TSH, and LH are separated do they have hormonal activity?
|
no
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what happens when TSH binds to specific membrane receptors in thyroid gland?
|
- activates adenyl cyclase
- thyroid growth and general metabolic activity increase including glucose oxidation, oxygen consumption, phospholipid synthesis and RNA synthesis |
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explain how TSH release is stimulated by hypothalamic thyrotropin releasing hormone (TRH)
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TRH promptly stimulates TSH secretion by a phospholipase C, IP3, DAG mediated process. TRH may also stimulate prolactin secretion
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TSH release is inhibted by what?
|
thyroid hormones acting directly on the pituitary
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estrogens have what affect on TRH receptors?
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increase the # of TRH receptors and thus increase pituitary sensitivity to TRH. although they do not stimulate TSH secretion, they modulate it by this effect on the pituitary
|
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what effect does alpha-adrenergic stimulation have on TSH secretion?
|
increases TSH secretion, cold induced stress probably increases TSH secretion this way
|
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gonadotropins influence maturation and function of what?
|
testis and ovary
|
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what are the 2 pituitary gonadotropins?
|
FSH and LH. A 3rd hormone, human chorionic gonadotropin (HCG), secreted by the placenta is chemically and functionally similar to LH
|
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1. what does FSH do in females?
2. in males? |
1. promotes growth of ovarian follicle and prepares the follicle for action of LH and enhances release of estrogen induced by LH
2. stimulates growth of the seminiferous tubules and early stages of spermatogenesis |
|
1. what does LH do in females?
2. males? |
1. stimulates final maturation of ovarian follicle, ovulation, and development of the corpus luteum. stimulates secretion of both estrogen and progesterone
2. stimulates secretion of testosterone by interstitial cells of leydig (has been called interstitial cell stimulating hormone - ICSH) |
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FSH and LH stimulate growth and function of their target by a ____________ mechanism
|
cyclic AMP
|
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gonadotropin releasing hormone (GnRH) acts directly on the pituitary to do what?
|
increase cAMP and gonadotropin release
|
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how would you describe the relase of GnRH from the hypothalamus?
|
puslatile
|
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do FSH and LH always rise and fall together?
|
no, b/c other factors such as sex steroids can also modulate the sensitivity of the gonadotropin-releasing cells
|
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LH secretion is inhibited by what?
|
testosterone and estradiol, both of which suppress GnRH
|
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what inhibits FSH secretion?
|
testosterone, progesterone, and possibly FSH itself; they act on the pituitary and perhaps on the hypothalamus
|
|
what hormone regulates the function of the adrenal cortex?
|
adrenocorticotropic hormone (ACTH)
|
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in women, the secretion of FSH and LH is _________
|
cyclic, w/ a rise just before ovulation (infradian rhythm)
|
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how does ACTH increase the synthesisi of steroid hormones?
|
by stimulating the conversion of cholesterol to pregnenolone via cAMP
|
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ACTH stimulates the growth of the _________
|
adrenal cortex
|
|
ACTH is synthesized as part of what larger, precursor protein?
|
pro-opiomelanocortin (POMC) which is selectivity cleaved in different cell types to yield a variety of bioactive peptides
|
|
what type of a molecule is ACTH?
|
a single chain polypeptide containing 39 AAs
|
|
ACTH secretion is controlled by what?
|
hypothalamic corticoptropin releasing hormone (CRH)
|
|
CRH is released in response to what?
|
a variety of stimuli including cold, hypoglycemia, pyrogens, epinephrine, estrogens or psychologic stimuli
|
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ACTH may inhibit CRH secretion how?
|
in a short loop feedback
|
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ACTH secretion is inhibited by what?
|
adrenal corticosteroids acting on both hypothalamus and pituitary
|
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ACTH undergoes a _________ rhythm peaking in the ________
|
circadian ; early morning
|
|
HGH (human growth hormone) is what type of molecule?
|
protein w/ a single chain of 191 AAs containing 2 intrachain disulfide bridges
|
|
the specific responses HGH provokes in target tissues are mediated by what?
|
cytokine receptor-JAK-STAT signal transduction pathway
|
|
are growth hormones the same in all species?
|
no, hormones from lower species have a different structure and are inactive in primates
|
|
IGFs are responsible for what?
|
many of the anabolic effects of HGH:
1. increased protein synthesis in both hard and soft tissues 2. increased bone matrix formation and calcification 3. increased AA uptake by m., bone matrix and kidney |
|
HGH stimulates production of what?
|
insulin-like growth factors IGF-1 and IGF-2 by liver and kidney
|
|
how does the action of growth hormone compare to that of insulin?
|
it is counter-regulatory to insulin b/c it is hyperglycemic (elevates blood glucose):
1. HGH antagonizes the effect of insulin on m. 2. HGH increases glycogenolysis, gluconeogenesis and glucose release from liver |
|
is growth hormone lipolytic?
|
yes, it stimulates hydrolysis of triglycerides and release of FAs from adipose tissue. Also stimulates uptake of FAs by muscle
|
|
growth hormone secretion is controlled by what 2 hypothalamic factors?
|
1. growth hormone releasing hormone (GRH)
2. growth hormone release-inhibiting hormone (GIH), also called somatostatin |
|
when somatostatin is injected what does it inhibit?
|
HGH, insulin, glucagon, FSH, and TSH
|
|
what are some examples of stimuli that cause plasma growth hormones to rise?
|
hypoglycemia, AAs, and exercise
|
|
plasma growth hormones follow a _______ rhythm w/ a peak in ________
|
circadian; early sleep
|
|
are HGH levels higher in men or women?
|
women b/c estrogens increase the sensitivity of this system to stimuli
|
|
what inhibits the release of HGH?
|
progesterone and adrenal corticosteroids
|
|
for prolactin to stimulate milk production in the mammary gland, the gland must have been properly stimulated by what?
|
female sex hormones estradiol and progesterone
|
|
besides estradiol and progesterone, lactation also requires that appropriate levels of what other hormones be present?
|
cortisol, thyroid hormones, and growth hormones
|
|
prolactin is a protein w/ structure similar to what?
|
HGH
|
|
prolactin secretion is stimulated by what?
|
prolactin releasing hormone/factor (PRF) and by thyrotropin releasing hormone (TRH), and also by estrogens and suckling
|
|
prolactin secretion is suppressed most of the time by what?
|
1. prolactin is under the direct neg. control of the tuberoinfundibular dopaminergic system. L-DOPA inhibits prolactin secrety by pituitary glands in vitro
2. also by prolactin releasing inhibiting factor (PIF) |
|
Ca++ is important in what various processes?
|
- membrane potentials
- enzyme regulation - blood coagulation - 2nd messenger function |
|
what % of the Ca++ is in the bone?
|
99%
|
|
in the ECF what % of the Ca++ is:
1. ionized? 2. bound to plasma proteins? 3. complexed w/ plasma ions? |
1. 50% (only form that is biologically active)
2. 40% 3. 10% |
|
what is the only form of Ca++ that is biologically active?
|
ionized
|
|
what effect does low Ca++ have on neurons?
|
it increarses neural excitability and may cause seizures
|
|
binding of Ca++ to plasma proteins is dependent upon what?
|
pH; acute alkalosis decreases binding and increases free Ca++
|
|
ECF Ca++ conc. is controlled by what 3 hormones?
|
1. PTH
2. calcitonin 3. vit. D3 (Mg++ and PO4- are somewhat controlled by these hormones) |
|
what is the 1/2 life of PTH?
|
2-5 min.
|
|
what type of a molecule is PTH?
|
84 AA peptide
|
|
PTH catabolism occurs where?
|
kidneys and liver
|
|
what are the 2nd messengers of PTH stimulation?
|
cAMP and Ca++
|
|
PTH helps to control what?
|
plasma conc. of Ca++, Mg+, and PO4-
|
|
what are the 4 ways in which PTH helps to control plasma conc. of Ca++, Mg+, and PO4-?
|
1. absorption of Ca++ and phosphate ions through PTH stimulation of renal vit. D3 secretion
2. stimulation of renal reabsorption of Ca++ and excretion of PO4- by kidneys 3. stimulates release of Ca++ and PO4- from canniculi fluid into ECF (osteocytic osteolysis - quick action) 4. acting through receptors on osteoblasts. PTH stimulates bone resorption by osteoclasts to release Ca++ and phosphate ions from bone into ECF (slow action) |
|
PTH stimulates bone formation that is coupled to what?
|
bone resorption - increases synthesis of growth factor IGF1 by osteoblasts
|
|
what stimulates vit. D3 synthesis by the kidneys?
|
PTH
|
|
what gland is calcitonin released by and what is the function of calcitonin?
|
released by thyroid gland; acts as an emergency break on bone reaborption by causing the osteoclasts to die
|
|
what does active vit. D3 do?
|
causes the intestine to absorb Ca++ and PO4-
|
|
what effect does a decrease in ECF Ca++ or increase in ECF K+ have on the parathyroid gland?
|
it stimulates the parathyroid gland to release parathyroid hormone which stimulates bone reabsorption to raise ECF Ca++ and PO4- release and stimulates kidney to reabsorb Ca++, excrete K+ and synthesize active vit. D3
|
|
1. osteoblasts are where?
2. osteoclasts are where? 3. what activates osteoclasts? |
1. in bone
2. in bone marrow 3. osteoblasts make them active |
|
why is PTH necessary for increased net bone growth?
|
b/c it is necessary for increased osteoblast #
|
|
PTH increases release of Ca++ and PO4- from bone tissue by what 2 mechanisms?
|
1. fast release by osteocytic osteolysis. ions already in solution w/i the canniculi are pumped out of bone
2. slow release by bone breakdown. bone is broken down by osteoclasts which release acid to dissolve HA and enzymes to break down extracellular matrix proteins. |
|
what stimulates osteoclast differentiation and activity?
|
PTH binding to receptors on osteoblasts
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hypertparahyroidism is usually caused by what?
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1. tumors
2. vit. D deficiency 3. low dietary Ca++ |
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symptoms of hyperparathyroidism
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- high plasma Ca++ and low PO4-
- bone reabsorption - decreased permeability of cells to ions - urinary stones and soft-tissue calcification may occur |
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what happens when there is a decreased permeability of cells to ions?
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nerve and m. membrane potentials increase:
- bradycardia (slow of heart) - arrhythmias - m. weakness |
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a low level of PTH can be caused by what?
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- atrophy of the glands
- autoimmune disease - accidental surgical removal - mutation (inborn errors of metabolism) |
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what are the symptoms of hypoparathyroidism?
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- low serum Ca++, meaning increased nerve cell membrane permeabillity and decreased membrane potentials (tetany)
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humans acquire vit. D3 in what 2 ways?
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1. ingested in diet
2. synthesized in skin |
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how is vit. D3 synthesized in the skin?
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- 7-dehydrocholesterol is photoconverted to previtamin D3 which spontaneously converts to vit. D3 which is inactive
- vit. D3 is hydroxylated to 25-hydroxy D3 in liver - in kidneys PTH stimulates 1alpha-hydroxylase (mitochondrial P450 enzyme) to form 1,25 dihydroxy D3 which is the active form of vit D3 |
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what are some other names for 1,25 dihydroxy D3?
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cholecalciferol, calcitrol
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how does active vit. D3 stimulate Ca++ and PO4- absorption from the intestinal tract?
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- this lipid soluble hormone binds to an intracellular receptor and increases gene activity
- active D3 turns on the gene for the synthesis of the Ca++ binding protein calbindin which aids Ca++ absorption - stimulates other genes 1. vit. D receptor 2. Ca++ pump 3. phosphate transporter 4. osteocalcin 5. alkaline phosphatase - inhibits PTH and IL-2 (has similar function on renal cells) |
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1. direct effects of active D3 on bone
2. indirect effects of active D3 on bone |
1. helps PTH in the multiplication and differentiation of osteoclasts and mobilize Ca++ out of bone. this raises ECF Ca++ levels
2. increases Ca++ and PO4- in ECF through its stimuulation of intestinal absorption, renal reabsorption and mobilization from bone. this increase in Ca++ and PO4- in ECF conc. increases mineralization of bone osteoid |
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Ca++ + PO4- = ?
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calcium phosphate (insoluble in H2O)
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as the conc. of PO4- increases the conc. of Ca++ will _________
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decrease
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leptin does what? secreted by what?
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stimulates less eating and inhibts bone formation; secreted by fat cells
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