Flashcards in Lecture 3 Deck (67):
Main functions of gonads:
Producing gametes - spermatogenesis/oogenesis
Producing sex hormones - testosterone/estrogen and progesterone
Secretes milky, slightly acidic fluid that makes up 50-75% of semen.
pH of semen:
Despite large acidic component from prostate, semen is overall alkaline to neutralize low vaginal pH.
March of the semen:
Spermatozoa are formed in seminiferous tubules. They flow to the rete testes and then to the efferent ductules, epididymis, and vas deferens.
An epithelium formed by Sertoli cells. Immature spermatogonia live at the periphery, and mature spermatozoa live near the lumen.
Where are Leydig cells?
Interstitial space around seminiferous tubules.
Where does maturation of spermatids into spermatozoa occur?
Hypothalamic pituitary axis:
Produces neurohormones called hypothalamic releasing hormones. Releasing hormones stimulate or inhibit pit gland hormone release. Also regulates circadian rhythm, sleep, fatigue, body temperature, hunger/thirst.
Pathway of hypothalamic releasing hormones:
From hypothalamus to anterior lobe of pit gland (adenohypophysis) through long portal vessels. From ant pit to other endocrine organs.
Post pit gland pathway:
ADH and oxytocin from hypothalamus go to post pit gland through median eminence and pituitary stalk. ADH and oxytocin then go to rest of body.
Hypothalamic control of adrenal medullae:
Preganglionic (sympathetic) motor fibres tell adrenal glands when to secrete epinephrine and norepinephrine.
GHRH: target cell, corresponding ant pit hormone, effect
Somatotrophs in liver. GH.
Stimulates IGF-1 production in somatic tissues, especially liver.
TRH: target cell, corresponding ant pit hormone, effect
Stimulates thyroid follicular cells to make corticosteroids.
CRH: target cell, corresponding ant pit hormone, effect
Stimulates fasciculata and reticularis cells in the adrenal cortex to make corticosteroids.
GnRH: target cell, corresponding ant pit hormone, effect -- FSH.
Stimulates ovarian follicular cells to make estrogens and progestins. Stimulates Sertoli cells to initiate spermatogenesis.
GnRH: target cell, corresponding ant pit hormone, effect -- LH.
Stimulates Leydig cells to make testosterone.
LH-targeting GnRH is inhibited by:
GnRH: target cell, corresponding ant pit hormone, effect -- PRL.
Stimulates mammary glands.
Effect of vasopressin:
Increases water permeability of renal collecting duct.
Effect of oxytocin:
Regulates uterus and breast.
Male hypothalamic pituitary axis:
Controls spermatogenesis in seminiferous tubules and androgen biosynthesis in Leydig cells.
Spermatogenesis and male hyp pit axis:
GnRH stimulates synthesis, storage, and secretion of gonadotropins (FSH and LH) by gonadotrophs in ant pit.
Where are GnRH neurons?
Dispersed through hypothalamus but localized in arcuate nucleus and preoptic area.
Synthesis and activation of GnRH:
Synthesized as inactive prohormone. Activated by cleavage.
Gonadotropin (LH/FSH) interaction with GnRH:
Gonadotropins have cell surface receptors with high affinity for GnRH. Receptors are coupled to G-protein G-alpha-q, which activates PLC.
PLC -> IP3 -> (Ca2+) and DAG -> PKC -> effect.
Releasing hormones that use PLC pathway:
Releasing hormones that use AC pathway:
CRH, somatostatin - increased.
Somatostatin again, GHRH - decreased.
GnRH secretion pattern:
Pulsatile! Means that LH and FSH are also pulsatile.
Dopamine signalling pathway through median eminence:
Decreased AC, increased K+, decreased Ca2+
LH feedback loop in hyp pit axis:
LH stimulates Leydig cells to synthesize (T).
(T) inhibits GnRH, which inhibits LH release.
FSH feedback loop in hyp pit axis:
FSH stimulates Sertoli cells to synthesize ABP, aromatase, growth factors, inhibin.
Inhibin inhibits FSH release.
Glycoprotein hormone family members:
LH, FSH, hCG, TSH.
Structure of glycoprotein hormones:
Alpha and beta polypeptide chains.
Alpha: all the same.
Beta: confer unique characteristics.
LH vs hCG:
Beta subunits are almost identical - hCG has 24 extra AAs and extra glycosylation at C terminus.
Where is hCG secreted?
Mainly placenta, also small amounts in testes and pit gland.
Immune reaction to fertilized egg:
hCG is responsible. Stops egg from implanting.
FSH/LSH, pre/post puberty: who dominates?
FSH before puberty.
LH after puberty.
Preference of male GnRH:
Prefers LH in adult human male.
Mature testes produce inhibin (inhibits FSH).
Pit gets more sensitive to gonadal steroid production (need less FSH).
LH in testes:
LH stimulates Leydig cells to synthesize and release (T). Primary source of (T). Leydig cells use steroid biosynthesis pathway to synthesized androgens from cholesterol.
LH in ovaries:
LH stimulates Theca cells to secrete (T). Granulosa cells convert testosterone to estrogen.
LH stimulates luteal function.
G-protein -> AC -> cAMP -> PKA -> effect.
Signalling pathway of LH:
LH and SCP:
LH stimulates synthesis of sterol-carrier protein (SCP). SCP-2 helps transport cholesterol from outer mitochondrial membrane to inner mitochondrial membrane. On the inner mitochondrial membrane, cholesterol sidechain is cleaved to begin stereogenesis (pregnenolone).
LH and SAP:
LH stimulates synthesis of sterol-activating protein (SAP). SAP also activates stereogenesis.
Molecule that inhibits testosterone transcription:
Stimulate Sertoli cells to synthesize and release ABP, inhibin, and aromatase.
ABP: secreted where? function?
Secreted into luminal space of seminiferous tubules. Keeps local (T) high.
Aromatase: where? function?
(T) diffuses into Sertoli cells from Leydig cells. Aromatase converts (T) into estradiol.
Growth factors and spermies:
Supports sperm cells and spermatogenesis. Increases number of spermatogonia, spermatocytes, and spermatids in testes. Possibly increases sperm motility.
Inhibin: family? structure? source?
Member of transforming growth factor beta (TGF-beta) gene family.
Glycoprotein heterodimer (alpha and beta) covalently linked.
Primary source: Sertoli cells and granulosa cells.
Crosstalk between Sertoli and Leydig cells:
Sertoli converts (T) to estradiol and diffuses into Leydig. Sertoli produces growth factors to increase LH receptors on Leydig cells.
(T) diffuses from Leydig to Sertoli.
For every LH/FSH released, another is synthesized and stored.
Conditions for optimal spermatogenesis: (5)
Leydig cells (1) and LH (2) produced testosterone (3). Sertoli cells (4) and FSH (5) produce inhibin and growth factors and nurse developing sperm.
Therapeutic use of hCG:
Initiate spermatogenesis in oligospermic men.
LH during puberty:
Produces androgens to make you a MAN
FSH during puberty:
Preferential release to control inhibitory effect on pit gland (using inhibin)
Where Leydig cells come from:
Mesenchymal tissue that surrounds testicular cords.
Converting cholesterol to testosterone in Leydig cells: 4 possible pathways. Gimme the best one.
1. Mitochondria. Cytochrome P-450 side chain cleavage (SCC) enzyme slaves long chain off of cholesterol to make pregnenolone. Rate-limiting step. LH increases enzyme affinity for cholesterol and stimulates SCC enzyme synthesis.
Then it's the chart you already know. (: (:
Tissues that can convert cholesterol to active hormone:
Adrenal cortex: cortisol, aldosterone, androgens.
Gonad: testosterone, progesterone/estrogen.
Transport of (T):
Almost never alone. Only free hormone is active!
45% of plasma (T) is bound to sex hormone-binding globulin (SHBG), aka TeBG.
55% is bound to corticosteroid-binding globulin (CBG).
2% is free.
What do ultrasounds look for to predict sex?
If DHT is present, it's a dude!
Secondary sex characteristics are dependent on [DHT or (T)?]
DHT! Not (T)!
(T) and aging: MENopause.
(T) declines with age. Decreased bone formation, muscle mass, facial hair, appetite, libido. (T) therapy can treat issues.
Metabolism of testosterone:
Liver: converts androgens to 17-ketosteroids.
Prostate: converts androgens to DHT.
Degradation products are excreted as water-soluble sulfuric acid or glucuronic acid conjugates, through urine or feces. Very little (T) gets through without metabolism.
Testicular descent: when? what happens?
Occurs in final month of fetal life.
Testes descend into scrotum to regulate sperm temp.
- Phase 1: testes move into inguinal region.
- Phase 2: abdominal wall herniates to gubernaculum (ligament between testes and labioscrotal fold).
- Phase 3: gubernaculum draws testes into the scrotum.