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225 Cards in this Set

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How does the hypothalamus signal to the pituitary?
Via blood vessels in the pituitary stalk
What is the hypothalamic/hypophyseal portal system?
From the hypothalamus to the anterior pituitary
How many hormone producing cells are in the anterior pituitary?
6
What type of neurohormones does the hypothalamus secrete to act on the anterior pituitary?
Releasing or inhibiting hormones
What are the glycoproteins?
FSH,LH, TSH, HCG
What are the steroids?
Aldosterone, Cortisol, Estradiol, Progesterone, Testosterone, Vitamin D
What are the amines?
Epinephrine, Thyroxine, Triiodothronine, Melatonin
What is the other type of hormone?
Polypeptide
What is an example of a non-hormonal feedback mechanism?
Increased calcium levels act on the parathyroid glands to stop them from releasing PTH- which results in a decrease in Ca.
What is an example of a hormonal feedback mechanism?
Cortisol acts on both the hypothalamus to stop CRH secretion, and the anterior pituitary to stop ACTH secretion which ultimately leads to lower cortisol
What type of tissue, histologically is that of the adenohypophysis?
Endocrine
What type of tissue, histologically is that of the neurohypophysis?
Neural
What are the six adenohypophysis hormones?
ACTH, GH, Prolactin, TSH, FSH/LH
What are the two neurohypophysis hormones?
Vasopressin (ADH) and Oxytocin
Where are vasopressin and oxytocin synthesized?
In two hypothalamic nuclei, the supraoptic nuclei and and paraventricular nuclei)
Where are vasopressin and oxytocin secreted and how do they get there?
They are transported via carrier molecules called neurophysins down the pituitary stalk to the posterior pituitary.
What are the two functions of oxytocin?
Parturition (increase uterus contraction in pregnancy) and milk ejection
What are the two structural components of the thyroid gland?
The follicle and the parafollicular cells
What is in the follicle?
Colloid
What is colloid?
Colloid is a major component of thryoglobulin
What does thyroglobulin contain?
The thyroid hormones
What are the thyroid hormones?
T3 + T4
What controls the synthesis of thryoglobulin?
TSH, released from the anterior pituitary
What do the parafollicular cells release?
Calcitonin
What is throxine (T4) made of?
Two diiodotyrosines (DIT)
What is triiodothronine made of? (T3)
One monoiodotyrosine (MIT) and one diodotyrosine (DIT)
What type of feedback does T3 and T4 exert?
They exert a negative feedback by stopping the synthesis of hypothalamic hormone TRH and the anterior pituitary hormone TSH
How does TSH act to promote T3 and T4 synthesis?
Induces activity of adenyl cyclase and the production of cAMP
How is a non-toxic goiter formed?
Iodine difficency, T3, T4 decrease, therefore no negative feedback on TSH, and the thyroid cells are stimulated- enlarged thyroid
How do T4 and T3 influence metabolism?
They increase the BMR (Basic metabolic rate)- increasing the breakdown of carbs, proteins and fats
How do thyroid hormones influence growth?
Without these, growth hormone cannot act to stimulate growth
What is thyroid required for with the CNS?
Brain development, stimulate synthesis of NGF( Nerve growth factor)
What are the three mechanisms by which thyroid hormones act?
Nuclear- effect proteins synthesis
At the inner mitochondrial membrane- increase O2 consumption
At plasma membrane, increase up take of aa's
What is Myxedema?
Primary hypothyroidism
What are some causes of PRIMARY hypothyroidism?
Atrophy of the thyroid
Autoimmune disease- Hashimoto
Non-toxic goiter
What is secondary hypothyroidism?
No synthesis of TSH by the anterior pituitary
What is tertiary hypothyroidism?
No TRH synthesis by the hypothalamus
What is infantile hypothyroidism?
No thyroid- dwarfism and cretinism similarities
What is Graves diseases?
A type of primary hyperthyroidism. It is when a TOXIC goitre is formed.
How is the toxic goitre formed?
It is an autoimmune disease where lymphocytes produce LATS (Long Acting Thyroid Stimulator) which mimic TSH
What is the second type of primary hyperthyroidism?
Thyroid cancer, where thyroid hormones are synthesized without TSH stimulation
What is secondary hyperthyroidism caused by?
No negative feedback of T3/T4- TSH synthesiszed. Pituitary tumor
What is tertiary hyperthyroidism caused by?
No negative feedback of T3/T4- TRH synthesized. Hypothalamic tumor
What is propylthiouracil?
It is an antithyroid drug that blocks the addition of iodine to thyroglobulin, can treat hyperthyroidism
What is PTH?
Parathyroid hormone, produced by the parathyroid glands increases the circulating levels of calcium
What does calcitonin do?
Lowers the circulating levels of calcium
What does Vitamin D do?
It increases the circulating levels of calcium
Where is calcium absorbed?
In the duodenum and jejeunum of the digestive tract
How does calcitonin decrease circulating levels of calcium?
Increases calcium deposition in bone
Increases kidney excretion of calcium into the urine
What is parathyroid hormone secreted from?
Parathyroid chief cells
Where are parathyroid glands located?
There are 4 on the back of the thyroid
How does PTH increase body calcium?
Promoting bone demineralization, Increasing Ca reabsorption in the PCT,
Stimulate conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (ACTIVE FORM)
Facilitate absorption of Ca from Gut
What controls PTH release?
Circulating levels of calcium
What type of mechanism does PTH use?
Second messenger (adenyl cyclase activation and production of cAMP)
What are some symptoms of HYPOPARATHYROIDISM?
Hypocalcemia, low production of active VD3, Tetany and convulsions
What are some symptoms of HYPERPARATHYROIDISM?
Besides obvious,
kidney stones
Severe: cardiac arrythmias, depressed neuromuscular excitability, calcium deposition on blood vessel walls, and cartillage
Why is Vitamin D not technically a vitamin?
It is synthesized from a cholesterol metabolite
What are the four steps to Vitamin D?
1- UV light combines with 7-dehydrocholesterol
2-25-hydroxylation in the liver
3- 1-hydroxylation in kidney
4- 1,25-dihydroylation by PTH
What are some functions of Vitamin D?
Increase Ca absorption in intestine, antinflammitory, anticancer
What is Rickets?
A form of Vitamin D diffiency, resulting in deficient bone mineralization. Can be caused by a lack of access to UV
Why is Rickets more severe in darker skinned people?
They have a skin pigment, melanin, that blocks UV.
What is osteomalacia?
Soft bone, can be caused by renal failure
Why would renal failure result in Vitamin D difficiency?
Decreased 1-hydroxylation in the kidney
Where are the adrenal glands located?
Adjacent to the upper surface of the kidneys
What are the two types of adrenal gland tissue?
The cortex and the medulla
What does the cortex look like?
Large, lipid containing epithelial cells
What does the medulla look like?
Chromaffin cells- fine brown granules when stained with potassium bichromate
What is the cortex derived from?
Mesoderm
Where is the medulla derived?
Neural Crest
What does the cortex?
Steroid hormones:
glucocorticoids, mineralcorticoids, and progestins
What does the medulla produce?
Catecholamines epinephrine and norepinephrine and some peptide hormones (enkephalin, dynorphin, and atrial natriuretic peptide)
What are the three layers of the Adrenal Cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What does the zona glomerulosa produce?
Mineralcorticoids
What does the zona fasciculata produce?
Glucocorticoids (cortisol)
What does the zona reticularis produce?
Glucocorticoids, progestins, androgens, and estrogens
Which areas of the adrenal cortex does ACTH control?
Zona fasciculata and zona reticularis
What is 18-alpha-hydroxylase present and what does it do?
Zona glomerulosa- key in synthesis of aldosterone (mineralcorticoid)
Where is 17-alpha-hydroxylase present and what does it do?
It is present in the zona reticularis and fasciculata- it is responsible in glucocorticoid synthesis
What does aldosterone do?
It increases the reabsorption of Na by the kidney
Affects loss of K+ and H+ which balance the reabsorption of Na
What do glucocorticoids do?
They have an effect on salt retention, protein and carb metabolism, and lipid metabolism, anti-inflammatory, immunosuppresive, lose calcium from bone leading to osteoporosis
How does glucocorticoid secretion lead to increased blood glucose levels?
Promotes gluconeogenisis by stimulating the release of gluconeogenis enzymes in hepaocytes. They also decrease glycolysis (glucose breakdown) and decrease cell glucose uptake
What type of diabetes can excess glucocorticoids lead to?
Adrenal diabetes
and eventually beta cell destruction leading to diabetes mellitus
What is propiomelanocortin?
Precursor to ACTH
What is congenital adrenal hyperplasia?
No cortisol production, ACTH is not inhibited by negative feedback- too much
How does ACTH perform its action on the adrenal glands?
Binds to a specific receptor on the membranes of the zona fasciculata and the zona reticularis- adenyl cyclase and cAMP production
Activates steroidogenic enzymes
What is the diurnal rhythm of ACTH and cortisol secretion?
The levels are minimum at midnight and maximum in the morning
Which disease can destroy this diurnal rhythm?
Cushing's disease
How does stress effect glucocorticoids?
Increase in release of CRH, Cortisol and ACTH
What is Addison's disease?
Hypofunction of the Adrenal cortex
Which disease can result in this hypofunction?
Tuberculosis
What is Cushing's diseased?
Hyperfunction of the Adrenal cortex
What is Cushing's diseased caused by?
Increased circulating levels of ACTH resulting in adrenal cortex hyperplasia
What is the percentage of the pancreas that is ENDOCRINE?
1%
What are the two cell types in the islets of langerhaans?
60% Beta cells and 25%alpha cells, detla cells, etc..
What do beta cells produce?
Insulin
What do alpha cells produce?
Glucagon
What do delta cells produce?
Somatostatin
What is insulin?
It is a hormone that works to DECREASE blood glucose
What is diabetes mellitus?
When beta cells are destroyed- glucose accumulates due to the inefficiency of most cells to take up glucose without insulin
What is used as an energy source?
Fat
What is the problem with using fat as an energy source?
Oxidation of free fatty acids are incomplete.
What is increased in circulation due to this incomplete free fatty acid production?
Acetoacetic acid, B-hydroxybutyric acid, and acetone
What is type II diabetes?
Hyporesponsiveness to insulin
What is a hypoglycemic coma?
Availability of glucose for the brain is not sufficient, blood glucose is only 20-30 mg/100mL
Which type of diabetes is associated with obesity?
Type 2. If you overeat, prolonged high insulin levels decrease the number of receptors in a process known as downregulation
What would the glucose tolerance test be like for a normal person/person with diabetes?
A person with diabetes has a lower glucose tolerance. After administering glucose to a NORMAL individual, levels return to normal after 2-3 hours. A diabetic individual will have a higher increase in glucose and it will take longer for the blood glucose level to go back to normal.
What are some body mechanisms to ensure proper levels of body glucose?
Beta cells sense body glucose levels
Gastrin and vagal impulses act to increase insulin before the meal even causes a rise in blood glucose.
What does glucagon do?
Raise blood sugar by promoting gluconeolysis and gluconeogenisis
Where is growth hormone produced?
In the anterior pituitary
What does growth hormone stimulate in the liver?
Somatomedins
What are somatomedins?
IGF 1 and 2. Can bind to insulin receptors also.
Increases growth and stimulates protein synthesis
Which two hormones regulate GH?
Growth hormone releasing hormone- stimulates release
Somatostatin- inhibits release
What is gigantism?
Excess of GH in YOUTH
What is acromegaly?
Excess of GH later in life (adulthood)
What are some symptoms of acromegaly?
many bones are LONGER and HEAVIER
What are the primary reproductive hormones in the male?
Gonads, testes
What are the primary reproductive organs in the female?
Ovaries
What are the two functions of gonads?
Gametogenisis (production of reproductive cells, gametes)
Secretion of sex hormones
What are the gametes in the male and female?
Spermatazoa in males
Ova in females
What are the sex hormones produced?
Testosterone- male
Estrogen and Progesterone in female
What stimulates development of gametes and secretion of sex hormones?
Gonadotropin releasing hormone is released in the hypothalamus and goes to the anterior pituitary where follicle stimulating hormone and lutineizing hormone are released.
What is a non-reproductive function of estrogen?
Prevents osteoporosis
What produces inhibin and what does it do?
Gonads- negative feedback on anterior pituitary
When does the male produce his gametes?
Constantly renewing the pool throughout his life to keep it constant
Where does spermatogenesis take place?
The seminiferous tubules of the testes
Where are Leydig cells located and what are they responsive to?
Outside the seminiferous tubules, and they are responsive to LH
Where are Sertoli cells located and what are the responsive to?
Within the seminiferous tubules, and they are responsive to FSH
What do Leydig cells synthesize?
Androgens
What do the Sertoli cells synthesize?
Androgen Binding Protein and inhibin
What is the dependence of spermatogenisis on androgen concentration?
In the seminiferous tubules, the concentration must be approximately 10 times higher than in circulation.
What does ABP do?
Ensures that this high concentration of androgens is attained in the seminiferous tubules
What is the hypothalamic-pituitary-leydig cell axis?
GnRH stimulates LH+ FSH- stimulate androgen release
Androgen inhibits GnRH, LH and FSH
What is the hypothalamic-pituitary-seminiferous-tubules axis?
inhibin inhibits FSH release ONLY
What are the functions of the ovary?
Production of mature oocytes and secretion of sex hormones
Do females continually produce oocytes like males continually produce sperm?
NO. At birth, ovary contains 2 million immature ova which are the whole lifetime supply.
How much ova are left at puberty?
400,000
What are oocytes surrounded by?
A single layer of granulosa cells, and a basement membrane
What are these oocyte/layer combinations called?
Primordial follicles
After an unknown initiating event, what do primordial follicles become?
Primary follicles
What is the growth of primary follicles controlled by?
Gonadotropins and steroid hormones
What is atresia?
Degeneration of follicles
What is the first layer that grows around the oocyte?
The Zona pellucida
What is characteristic about the formation of primary follicles?
The granulosa cells divide and increase in layer number
What are FSH and estrogens important for in this step?
Influencing the granulosa cells division
What is estrogen involved in?
Expression of LH receptors on the surface of granulosa cells
What is the difference between a primary follicle and a secondary follicle?
Secondary follicle has receptors for LH, FSH, and estrogen. It has an antrum which contrains the secretions of the granulosa cells
What happens to form the preovulatory follicle?
Granulosa cells elaborate follicular fluid. This is the mature follicle
What are theca cells?
Steroid producing cells that are formed from stroma surrounding the follicle differentiating.
What do these theca interna cells do?
Collaborate with granulosa cells to increase the synthesis of estrogen
Why does follicular atresia take place?
So that only one oocyte will ovulate per cycle
What is ovulation?
Follicular rupture and release of oocyte
What is a ruptured follicle transformed into?
The Corpus Luteum
What does the corpus luteum secrete?
Progesterone
What would prevent the dropping off of huge levels of estrogen and progesterone production by the corpus luteum?
Implantation of fertilized ovum
If implatation occurs, what is the corpus luteum transformed to?
The corpus luteum of pregnancy?
What is the corpus luteum of pregnancy responsible for?
Synthesis of progesterone and estrogens and proper endocrine environement for pregnancy until this role is taken over by the placenta
What induces luteal regression and how?
Prostaglandins may play a role. They do this by decreasing LH binding.
What does luteal regression result in?
A decrease in plasma estrogen and progesterone which could stimulate the next reproductive cycle
What happens before the first day of the menstrual cycle?
The endometrium (lining of uterine cavity) proliferates due to the presence of estradiol
What does progesterone induce?
Appearance of glycogen secreting glands
What happens at Day 1?
First day of detectable vaginal bleeding- deterioration of uterine endometrium
What are the levels of estradiol and progesterone when bleeding begins?
Low
What do these low levels lead to?
Increased levels of FSH release from anterior pituitary
What do normal levels of estradiol do?
Block FSH release
What also contributes to the rise of FSH during the 5 days of bleeding?
Decrease in inhibins
What does the increased FSH do?
Follicles develop. FSH stimulates the granulosa cells to proliferate
What does this proliferation of granulosa cells lead to?
Estrogen
What happens at day 8?
1 follicle is dominant, others degenerate by atresia
What does the increased estrogen cause?
Uterine endometrium proliferation
What is the endometrium like at day 13?
Very thick
What happens at this point under the influence of estradiol?
Induction of progesterone receptors into the endometrium
What does moderate estradiol do?
Negatively feedback on FSH release
Stimulate LH synthesis
Block LH release
Increase pituitary sensitivity to GnRH
What do elevated estradiol concentrations do at day 14?
Stimulate LH release- resulting in an LH surge (LH had built up in pituitary area because it had been blocked from release)
What are the two feedback mechanisms that estrogen is involved in?
Negative on LH release
Positive on GnRH sensitizing resulting in a higher LH synthesis
What does the LH surge cause?
Follicle to rupture and ejection of ovum
How do oral contraceptives work?
They maintain moderate levels of estrogen and progesterone suppress release of LH and FSH and thus follicle maturation and ovulation
What happens to the endometrium under the influence of progesterone?
It becomes glandular, it is ready to receive the embryo
What happens in the luteal phase?
14 days- luteolysis occurs, if no implantation, steroid hormone levels drop, endometrium degenerates menstruation begins
At ovulation, what happens to the unfertilized egg?
It is taken by the fimbria of the oviduct (fallopian tube) and is propelled towards the lumen of the uterus
How does fertilization occur?
Sperm will travel in the fallopian tube and will fertilize the egg.
What happens to the fertilized egg as it is transported from the oviduct to the uterine lumen?
It develops to the blastocyst stage
What does the blastocyst differentiate into?
The trophoblast and the inner cell mass
What will the trophoblast become?
The placenta
What will the inner cell mass become?
The embryo
What does the trophoblast secerete around the time of implantation?
Human chorionic gonadotropin
What does HCG do?
It has LH like properties and stimulates the corpus luteum to continue secreting hormones
What happens at the 12th week of pregnancy?
The placenta takes over the endocrine function of the corpus luteum
What is the fetoplacental unit?
The fetus + placenta form this
What does the fetal liver acquire?
Important function in estrogen synthesis
What does the placenta produce?
Human chorionic somatotropin, relaxin and progesterone
What forms the basis of the pee test for pregnancy?
HCG- appears quickly in the urine after impregnation
What is lactation?
The secretion of milk by the breast
What is progesterones role in lactation?
Stimulation of alveoli formation
During pregnancy, what hormones influence the formation of ductal and alverolar structures?
Estrogen, progesterone, prolactin and human placental lactogen
What hormones are responsible for mammary gland growth?
GH, cortisol and thyroxin
What is responsible for milk production in pregnancy?
Prolactin
What is responsible for preventing milk ejection during pregnancy?
High estrogen levels
What is lactational amenorrhea?
During nursing, FSH and LH secretion is inhibited and the entrance of the reproductive cycle is blocked.
What is menopause?
The loss in steroid hormone production
What causes this?
Depletion of follicles
What causes the high release of FSH and LH in pregnancy?
The stopping in steroid hormones eliminates the negative feedback loop that is normally placed on FSH + LH
Can fertility be restored by hormone replacement therapy?
NO. Primary reason for menopause is the depletion of follicles
What are some substances that use nuclear signalling?
Small lipophillic molecules and glucose
Which substances use membrane receptors that result in nuclear signalling?
Peptide hormones, small hydrophillic molecules
How do nuclear receptors exert their effects?
Regulating transcription of genes, leading to a change in protein levels
What is PXR used to screen for?
The capacity of small molecule drug candidates to activate their own metabolism and the metabolism of other drugs
What happens to drugs that potently activate PXR's?
They are eliminated from development. You don't want drugs to metabolzie themselves
What do PPAR's do?
Control lipid metabolism and adipogenisis
What are the three PPAR receptors?
alpha beta and gamma
What does PPAR stand for?
Peroxisomal proliferator activator receptor
Where PPARalpha receptors most highly expressed?
In tissues that display high rates of fatty acid metabolism
What do PPARalpha receptors bind?
Fatty acids and their metabolites
How can fatty acids control their own metabolism?
Through PPARalphas, by inducing the expression of genes encoding metabolic enzymes required for fatty acid catabolism (breakdown)
Where are PPARgamma receptors most highly expressed?
Adipose tissue, intestine, and spleen
What is a high affinity ligand for PPARgamma
thiazolidinedione
What type of drugs were TZD's initially developped for?
Anti-diabetic drugs
What is the real essential function of PPARgammas?
Apidogenisis
How then, do PPARgammas stimulation allow TZD's to be anti diabetic?
They remove free fatty acids, therefore forcing the cells to rely on glucose for metabolism
What does FXR control?
Bile acid metabolism
How is cholesterol metabolism controlled?
Feedforward mechanism, production of CYP7A, enzyme to convert to bile acids
Feed back- elevated levels of bile acids inhibit bile acid synthesis
Where is FXR orphan receptor most highly expressed?
Liver and intestine
What is FXR activated by?
The primary bile acid chenodeoxycholic acid
Why are bile acids important?
They represent solubulized excreted forms of cholesterol
They are both fat and water soluble, they function to facilitate absorption of fats and fat soluble vitamins in the small intestine
What are two pieces of evidence that FXR is a bile acid receptor?
1- bile acid bound FXR represses CYP7A synthesis- demonstrates feedback mechanism
2- FXR activates expression of intestinal bile acid binding protein
What are some diseases that have demonstrated north-south gradients?
Colon + prostate cancer, Crohn's disease, MS (autoimmune diseases), infectious diseases