Endocrinology Final

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Parathormone

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Secreted by parathyroid. Peptide. Increases blood Ca+. Aids in bone resorption, increases gut uptake and absorption, and decreases Ca+ clearance by increasing phosphate secretion pools.

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Calcitonin

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Secreted by C-cells. Lowers blood calcium. inhibits PTH action (inhibits demineralization)

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C-cells

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secrete Calcitonin, located in Thyroid.

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CT structure

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S--S disulfide bond essential for impactivity

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bioassay

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test the relative potency for a substance, like a hormone or vitamin, by testing its effect of growth on an organism.

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Blood [Ca+] bioassay

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1. Inject CT
2. measure [Ca+] in blood
--salmon CT 20-50x, ~5000x more effective in a mouse than in human.
lowers [Ca+]

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CT/PTH bias

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CT more effective at lowering [Ca+] than PTH is at raising [Ca+]
-PTH requires 2 micrograms for ^ 1mg/100mL blood [Ca+]. CT requires .001 micrograms for v 1 mg/100 mL blood [Ca+].

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Vitamin D3 actions

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synergizes actions of PTH; reduces number of PTH receptors, but also increases [Ca+] uptake.

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Cortisol actions

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Stimulates PTH hypercalcemic effects

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Other Actions of CT

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Increases HCl secretion in the stomach

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Other actions of PTH

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hypotensive action--lowers BP, vasodilation. ^ heart rate, v and ^ stroke volume--->cardiac output.

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Ca+ deposits

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Acellular Bone, celluar bone, soft tissue

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FSH (male)

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increases spermatogenesis, increases ABP

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LH (male)

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increases androgen production and release

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PRL (male)

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increases Leydig cell sensitivity to LH (upregulates LH receptors)

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MIH

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during embryonic development (degeneration of duct system)

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inhibin

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inhibit FSH release, thereby increase LH

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CO-culture

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pituitary fragment, sertoli cells ---> decrease in FSH release into culture medium. If the seritoli cells are replacd with dispersed letvin cells, no decresed effect on FSH.)

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Androgens (roles)

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1. Primary male hormone --induction/differentiation duct male system. seminal vesicals, prostate.
2. promotes secondary sex characteristics (antlers, shape, etc)
3. Spermatogenic --works with FSH --proximate mediator of germ cell maturation
4.protein metabolism (anabolic)
5. increase in RBC production (increases oxygen carrying)
6. CNS respriatory effects (increases MR)
7. behavior

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Mechanism of action of androgen

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"classic" -- injection of androta increases mRNA and globulin, but a goloduectomy decreases both.

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Follicle layers

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1. fluid-filled antrum
2. granulosa cells -- responsible for steroidogenesis
3. theca interna - acetate --->into testosterone (steroidogenic)
4. Corpus luteum - (formed from follicular reminants)

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GnRH (females)

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stimulates both gonadotrophs and follicular fluid (LH and FSH)

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LH (females)

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Required for: Antrum formation, follicular disruption, corups ludeum formation, stimulating progesterone, facilitates reorganization of the follicle.

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Hormones from hypothalmus for reproduction

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GnRH --->Stiumlates FSH, LH

dopamine--> inhibits PRL

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Pituitary hormones for reproduction

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FSH, LH, and PRL

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Gonadal hormones for reproduction

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Inhibin inhibits FSH, estrogen inhibits FSH, inhibits and stimulates LH and stimulates PRL, progesterone inhibits LH, and early stimulates PRL, later inhibits PRL.

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Ovarian Life cycle (non-pregnant)

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Increased LH -->positive feedback mechanism (LH surge) luteotropic
---E2 produced, progesterone
---everything ceases, and E2 levels drop, and stimulates proliferation of uterus. (endometrial apoptosis)

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Ovarian Life Cycle (pregnant)

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PRL is stimulates and E2 levels remain high while Progesterone levels remain low to maintain uterus.

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Estrogen Actions (females)

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Oogenesis, uterin proliferation, modulates functional development of female duct system, proper reproductive behavior, growth and development of female reproductive system

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Progesterone

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increased uterine secretion, oocyte mediator and germ cell maturation

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Gonadotrophin

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Stimulates oocyte maturation. Excreted from pituitary.

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Maturation Promotion Factor

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isolated in carp, aids in maturation of oocytes.

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Hormone Produced by Leydig

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Testosterone

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Two major functions of testis

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spermatogenesis, androgen production

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Signalling pathway of hormone controlled testicular function

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Neural signal-->pulsatile secretion of GnRH--> conveyed to anterior pituitary --> gonadotropins (LH and FSH) circulate and bind to Leydig and Sertoli cells--> LH stimulates steroidogenesis and testosterone secretions from Leydig cells --> FSH suppors spermatogenic activity of sertoli cells.

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Inhibin/Activin

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Inhibin is shown to inhibit FSH actions and thereby reducing spermatogenesis; Activin is shown to activate FSH.

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Gonadal feedback mechanism

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androgens exert a tonic inhibitory feedback mechanism on pituitary gonadotropin secretion

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sexual behavior

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regulated by preoptic area and hypothalmus; INAH 3 *

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Agressive behavior

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regulated by testosterone; castrated rats showed less aggressive behavior

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Various Androgen effects on the body

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1. Reproductive glands produce semen. 2. Androgen activates sebaceous glands/stimulates hair follicles. Can also cause hair to fall out. 3. Hihfer kidnery activities of C oxidase and lysosomal hydroxylases. 4. NGF and EGF submaxillary glands acutely controlled by androgens. 5. Birds can develop brood patches 6. Eopdermal Cornifications. 7. Antlers. 8. Breeding Terbercles. 9. Growth of skeletal muscle

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Estrogen roles in males

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1. Increases sperm counts 2. aids in illeciting sexual behavior 3. Aids in growth and fusing epiphises 4. Cardiovascular functioning.

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Androgen receptor pathway

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Testosterone -->5 alpha reductase --> dihydrotestosterone--> Androgen --> Androgen receptor --> Dimerization --> Transcription --> mRNA --> Translation --> Protein

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Antiandrogens

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derivitives of progesterone --> inhibitory of testosterone because of receptor occupancy.

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Erection response hormones

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NO, VIP, and prostoglandin E

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FSH/LH in ovulation development

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LH appears in the theca, is present in the beginning stages of luteal cells. FSH acts on granulosa in latter stages of preovulatory development. LH coincides with and increase in estrodiol, and FSH coincides with an increase in progesterone.

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Theca interna actions

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Convert C27 to C19 (androgens)

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Granulosa actions

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Convert androgens to estrogens

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Antiestrogens

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nonsteroid compounds that prevent the actions of estrogens on target tissues. Future medicines hope that development of new selective estrogen receptor modulators can provide potential for tretment for mammary tumors, osteoporosis and menopausal symptoms.

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feedback system of estrogen and progesterone

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Initially, low levels of estrogen have negative feedback on LH. Then elevated levels of estrogen from developing follicle develop positive feedback. Positive feedback of progesterone ensues upon ovulation. Corpus luteum reestablishes negative feedback of progesterone.

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Follicle development and oocyte maturation

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induced by LH and FSH

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Inhibin secretion induction

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FSH stimulation (negative feedback)

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Ovulation cycle

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Neural pulses-->GnRH release --> Anterior pituitary --> LH levels increased during follicular phase --> Estrogens increase --> FSH secreted --> Progesterone levels increase

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Amenorrhea

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absence of monthly menstral flow, whether a natural occuring phenomena or related to pituitary gonadotropin secretions

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Premature Ovarian Failure

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recognized as a type of amenorrhea of two different classifications: a pituitary gonadotropin disturbance when LH or FSH doesn't interact with the follicle or total depletion of the follicles.

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Polycystic Ovarian Disease

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hyperandrognemia, polycystic ovaries, can cause infertility, usually results in obesity, and is genetic.

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Hirsutism

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The presence of hair on women on areas of the body where is shouldn't be. Hyperandrogenic condition.

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PL

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Aids in Milk production--secreted from placenta

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Neural tropic growth factors

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peptide growth factors that regulate the growth and differentiation of the CNS and PNS--> may be ecological basis of disorders --> Alzeimer's disease.

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NGF

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Uesd for growth. function, and development of neural cell. Made by many cell types ( epithelial, smooth muscle, fibroblast, Schwann cells )

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EP functions and mediators

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renews and replaces RBC, thus raising O2 content. Increased in response to growth hormone and in response to androgen stimulation.

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Polycythemia

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above-normal red cell number can be caused by increase in EP production

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anemia

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can be caused by inactive EP

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Thymosin actions

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located in thalmus; appear to trigger maturational progression of T-cell development so T-cells can respond to antigens.

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PDGF

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released from platelets during aggregation of clot formation. May be to initiate growth of surrounding cells at site of wounding in response to thrombin.

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EGF

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enhances cell proliferation in the epidermis. Increases growth of fetal pulmonary epithelium. Stimulation of DNA synthesis in digestive tract. Acceleration of healing wounds. When injected with this, eyelids open and teeth breakthrough prematurely

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EGF control

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Controlled by nervous system; secreted by salivary glands

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Angiogenic factors

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promote blood vessel growth

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Fibroblast Growth Factor

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heparin binding avidity, ability to promote angiogenesis, mitogenic activity towards cells of epithelial, mesenchymal, and nerual origin. Development, tissue repair, maintenance of neurons, pathogenesis of disease.

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FGF endocrine type

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autocrine; inducing angiogenesis into the tumor proliferating tumor growth

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Describe the difference between TGF alpha and TGF beta

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TGF alpha is similar to EGF in that it acts in dermal regerneration. Transforming growth Factor beta, however, aids in regulating growth upon stimulation of estrogen.

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Cytokines roles and example

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synthesized by immune and non-immune cells. Mediate intercellular communication including growth and differentiation, cytolytic, chemotactic, and immunoenhancing. I.E. interleukins.

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IGF I vs IGF II in neonatal growth

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IGF-I is important in post-natal growth whereas IGF-II is more important in pre-natal growth.

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TSH effects on Thyroid

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Increased quantity and activity of follicular cells-->Cells become columnar in shape luminal content of colloid is greatly decreased.

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pathway of TSH

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TSH interacts with follicular cells resulting in adenylate cyclase and cAMP production.

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DIT/MIT pathway

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incorporates iodine in order to create T3 (DIT and MIT) and T4 (DIT and DIT). These molecules compose thyroglobulin, and such activities are stimulated by TSH.

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iodothyronines

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Thyroid hormones stimulated by iodine--such as T3, T4, T2, T1, T0.

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Thyrotropin Releasing Hormone actions

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Controls the secretions of TSH. Feedback mechanisms are located at the pituitary in order to control TSH and TRH secretions. Released by the hypothalmus.

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TSH and TRH mechanism

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require a binding protein in the cytoplasm and cytosol to gain access to nucleus.

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Factors that increase T3 and T4 thyroid hormones

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Thermogenesis --> T3-induced Na+/K+ATPase activity pump causes a rise in heat by rise in enzyme rather than affinity. increase in caloric intake can alter T3 levels.

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Tissue expansion

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includes hypertrophy, hyperplasia, and differentiation

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tissue regression

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includes programmed cell death (atrophy)

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Growth Hormone

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mediated by sulfation, released by pituitary

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GH pathway

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Brain --> GHRH + Somatostatin - ---> Pituitary releases GH --> Liver releases IGF - I --> acts on target tissues

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Stimulators of GH

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Fasting, NPY, CCK, DA, TRH, GnRH, and GHRH

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Inhibitors of GH

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SS, NE, 5-HT, and IGF-I

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Somatostatin effects on growth

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Decreases organismal growth, IGF-I and GH

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somatostatin signaling pathway

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variety of pathways; inhibits IGF-I and GH via MAP-K pathway

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Endocrine disrupting compounds

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Natural and synthetic hormones, phytoestrogens (in foods), organochlorines (pesticides), alkyphenol polyethoxylates, (pesticides, detergents), dioxins (cumbustion product), bisphenol A (plastic, resnins)

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Endocrine disrupting compound abnormalities

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developmental abnormalities, growth disruption, reduced tolerance to stress, and tumorogenesis

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Factors that transform cells

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hereditary defect, spontaneous mutation, chemical-induced mutation, radiation-induced mutation, viral infection

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seminiferous tubules

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contain germinal epithelium and sertoli cells

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germinal epithelium

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gives rise to germ cells (spermatozoa) through mitosis, meiosis, and differentiation

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sertoli cells "nurse cells"

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serve as "nurse cells" to developing germ cells by providing nutrition, and producing androgen binding protein, GnRH, MIH, and Inhibin.

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ABP metabolic pathway

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cAMP

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Primary roles of androgen and estrogen

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development of male and female sex characteristics

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Oxytocin

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increases myoepithelium contraction and results in milk let down. Increase in uterine contractions.

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parturition process of hormones

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Relaxin opens up pubic girdle. OT causes uterine contractions, prostoglandins increase luteolysis, and decrease progesterone, altered E/P ratio. Increased endometrial excitability.

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FSH (females)

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stimulates follicle growth and follicle fluid production