Reproduction 2 Flashcards
Explain the primary regulatory mechanisms of the HPG axis.
Describe the main pituitary hormones and their effects.
Major hypothalamic hormone:
Gonadotropin-releasing hormone (GnRH/LHRH)
Absolutely required
Must be released in a pulsatile manner
Major pituitary hormones = Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH). LH: stimulates steroidogenesis in ovaries and testes. FSH: stimulates gametogenesis (egg and sperm maturation) in ovaries and testes.
Slide 5
Describe Kisspeptin in regards to the regulation of GnRH?
What is its receptor? Would would mutation in this receptor cause?
Kisspeptin – required to initiate increased GnRH release at the time of puberty. Presumed signal for pubertal onset.
Mutations in KISS1 receptor cause hypogonadotropic hypogonadism
What effect will androgens/estrogens (gonadal steroid hormones) have on GnRH?
Gonadal steroid hormones (androgens/estrogens) – exert negative and positive feedback on GnRH
Describe how the following will affect GnRH:
GnIH prolactin neutrotransmitters (GABA) cortisol (stress) growth factors (TGF alpha/beta) neuropeptides (opiods, melatonin)
almost all inhibit GnRH
What does Inhibin B do? Where is it expressed? Describe how it works.
INHIBIN B – specific inhibitor for FSH
Expressed in gonads
Inhibits FSH beta subunit synthesis in gonadotropes
Slide 7
Where is activin expressed?
What does it do? Where does it act?
ACTIVIN –
Expressed in pituitary and gonads
Stimulates FSH beta, LH beta, and GnRH receptor synthesis in pituitary
Slide 7
Describe the major physiological actions and regulation of the pituitary gonadotropin hormones, LH and FSH, in male reproduction.
…
Describe:
PITUITARY GONADOTROPINS “TROPIC HORMONES”
Describe their structure and what they have in common.
Large glycoproteins
Share a common alpha subunit
Beta subunits specify hormone: LH, FSH, TSH
What do LH and FSH do in men and women?
IN GENERAL FOR BOTH SEXES:
LH – stimulates steroidogenesis
FSH – stimulates gametogenesis
In regards to male production, what will FSH stimulate?
What do they act on?
Sertoli cells – have high affinity FSH receptors
Form the blood-testes barrier
FSH –
Stimulates spermatogenesis
Increases sperm motility
Stimulates growth of seminiferous tubules – primary determinant of testes size
Stimulates androgen binding protein (ABP) – maintains high local T
Stimulates aromatase
Stimulates inhibin
Stimulates growth factors
Slide 10
What effect will LH have in male reproduction processes. What will LH stimulate (what cells have LH receptors?)
Leydig cells – have high affinity LH receptors
LH –
Stimulates steroidogenesis from cholesterol
Androgens = 19 carbon steroids
Stimulates StAR protein – rate limiting
Stimulates Leydig cell growth
Describe the type of horomone: androgens
19 carbon steroids
Distinguish between direct actions of testosterone and the actions mediated by DHT and E2 and identify the roles of aromatase and 5α-reductase in steroid metabolism.
…
Where are testosterone precursors made?
Testosterone precursors made in extragonadal tissues: brain, adrenal, skin, adipose tissue
What is the primary source for circulating T?
How does T travel in circulation?
What happens to it intracellularly?
Metabolized?
Testes – primary source of circulating T
Circulation – bound to SHBG
Intracellular – converted to estrogens or DHT
Metabolized – diols, triols
What type of receptor do T and DHT bind? Which has a higher affinity for it?
T and DHT both bind androgen receptor (AR)
Nuclear steroid receptor
DHT higher affinity than T for AR
Describe the excretion of testosterone.
How much is excreted as free testosterone?
What happens to T that is not excreted?
less than 2% of daily production is excreted as free testosterone
Remainder is converted to 17-ketosteroids & DHT
conjugated to water soluble forms and excreted.
What does masculinization of the brain require?
Masculinization of the brain requires T to E conversion
Describe the role of DHT.
Slide 15
Compare testosterone and DHT actions in regards to fetal development.
Fetal development:
T- epididymis, vas deferens, seminal vesicles
DHT- penis, penile urethra, scrotum, prostate
Describe the role of T and DHT in pubertal development.
T- penis, seminal vesicles, musculature, voice, skeleton, spermatogenesis
DHT- scrotum, prostate, male pattern hair distribution, beard, balding, diamond-shaped, pubic escutcheon (instead of triangle), sebaceous glands
Describe the gross anatomy of the male reproductive system.
Penis
Accessory glands
Testes
PENIS
Glandular and muscular tissue
Penile urethra
ACCESSORY GLANDS
Seminal vesicles
Prostate gland
Bulbourethral gland (Cowper’s gland)
TESTES
Seminferous tubules
scrotum
Explain the significance and process of testicular descent and describe cryptorchidism.
Cryptorchidism – “hidden testis”
Most common congenital abnormality of urogenital tract
Often result of undescended testes that remain in abdominal cavity
Testes descent maintains lower temperature (1-2 degrees below core body temp)
- embryonic position
- transabdominal phase (8-15 week) anchoring
- inguinoscrotal phase (25-35 wk) migration
- elongation of cord (0-10 years)
Describe the model of counter-current transfer of heat or a substance from the venous blood in the pampiniform plexus to the blood in the testicular artery.
Slide 21 Spermatic cord: ductus deferens gonadal artery gonadal vein
Model of counter-current transfer of heat or a substance from the venous blood in the pampiniform plexus to the blood in the testicular artery. The testicular artery also supplies the caput and part of the corpus of the epididymis.
Describe the functional anatomy of the testis.
How much does each testis weigh?
What is it composed of?
How much sperm prod. per day?
Each adult testis weighs approx 40 grams with 80% germinal tissue and 20% supportive connective tissue with Leydig cells.
Seminiferous tubules are about 200 meters of coiled mass.
100 – 200 x 106 sperm per day (oligospermia is
In regards to testes, what is inside peritubular space?
What is inside intratubular space?
Peritubular space = Leydig cells, myoid cells, blood supply
Intratubular = Sertoli cells, developing germ cells, lumen
Compare and contrast the roles of Sertoli and Leydig cells and describe their interdependence.
Leydig - sertoil cell interactions
Sertoli cells form tight junctions to create blood-testis barrier
High T concentrations in lumen support sperm development
Slide 25, 27
Describe PARACRINE ACTIONS OF INHIBIN AND ACTIVIN IN TESTES.
How does Inhibit affect LH induced testosterone production? How does activin affect testosterone production in Leydig cells?
Inhibin (αβ) augments LH-induced testosterone production in Leydig cells.
Activin (ββ) inhibits testosterone production in Leydig cells
NOTE: Opposite of action they are named for in pituitary
Distinguish between the different processes associated with spermatogenesis.
Stermatogenesis-
Spermiogenesis-
Spermiation-
Spermatogenesis – the process by which spermatogonia become 4 haploid spermatids
Spermiogenesis – maturation of spermatids into spermatozoa
Spermiation – release of spermatozoa from Sertoli cells into lumen.
All processes occur in the seminiferous tubules.
Slide 29, 30
Describe the structure of mature spermatozoa.
Maturation of spermatozoa continues after release into the lumen
Spermatozoa initially immobile – passive movement from seminiferous tubule to rete testis.
Spermatoza mature along the single tubule of the epididymis
Slide 31
Describe sperm maturation.
What is formed and what is contained in this structure?
Receptors must be aquired for what purpose?
How does cytoplasm and cell volume change?
When is maturation complete?
Progressive increase in motility
Formation of acrosome: sperm “cap” containing hydrolyzing enzymes used to penetrate ovum.
Acquisition of receptors necessary for binding to ovum.
Deceased cytoplasm and cell volume.
*maturation not fully complete until sperm enter vagina (capacitation)
Explain the roles of accessory glands in male reproduction.
Describe semen.
SEMEN = (slide 35)
10% sperm (150-600 million)
70% fluid from seminal vesicles
10% fluid from epididymis, prostate, bulbourethral glands
Explain the roles of accessory glands in male reproduction.
Describe seminal vesicles.
What is it paired with? What does it form?
What nutrients are present?
pH? How does pH affect processes?
SEMINAL VESICLES =
Paired; with inferior bladder
forms the ejaculatory duct
Fructose, citric acid, other nutrients
pH – seminal vesicle fluid makes semen more alkaline (~7.3-7.7) promotes optimum motility and survival
Explain the roles of accessory glands in male reproduction.
Describe prostate gland.
What does it surround?
What does it secrete?
What are its enzymes important for?
PROSTATE GLAND =
Surrounds prostatic urethra
First fluid to be expelled in ejaculate
Secretes factors that prevent clumping of sperm
Proteolytic enzymes important for liquefaction of semen
Describe benign prostatic hyperplasia.
How does prevalence change with age?
Describe PSA. (What do low “free” PSA levels indicate?)
Describe the pathology.
Prevalence increased with age:
31-40 year old – 8%
51-60 year old – 50%
>80 year old – 80+%
Prostate specific antigen (PSA) – useful diagnostic for increased prostate growth. Increase is normal with age, but higher than normal can indicate prostate cancer. “Free” PSA is lower in cancer compared to benign.
Pathology unclear. Some evidence for higher estradiol:testosterone ratio as men age. Possible increased sensitivity to testosterone due to increased androgen receptors.
Explain the roles of accessory glands in male reproduction.
Describe bulbourethral gland.
BULBOURETHRAL GLAND
Also called Cowper’s gland
Immediately below prostate
Secrete mucous into urethra upon arousal – pre-ejaculate
Contrast sympathetic and parasympathetic control of male sexual function.
(Flaccid state)
What arteries? Parasym/sym control?
Helicine arteries contract – restricting blood flow in flaccid state. Controlled by tonic sympathetic activity.
Describe an erection.
Describe muscle/blood flow changes?
ERECTION
Relaxation of vascular smooth muscle (corpora cavernosa and corpus spongiosum) leads to increased blood flow in cavernous tissue
Engorgement compresses outflow pathway and creates tumescence (swelling)
Ia an erection primarily under parasympathetic or sympathetic control?
Describe the processes. What do postganglionic nerves release?
What effect with those hormones have?
Erection is Primarily Under Parasympathetic Control
Parasympathetic postganglionic nerves release Ach and NO
Ach can bind muscarinic receptors and activate PLC (via Gαq). This increases calcium and activates NO synthase
NO activates guanylyl cyclase
What effect does Viagra have?
Describe mechanism and result.
VIAGRA (sildenafil)
Inhibits phosphodiesterases that would normally decrease cGMP
Maintains chronic state of vasodilation
Not specific to penile circulation – can cause heart problems
Still requires CNS arousal
Erection is Primarily Under Parasympathetic Control.
Sympathetic nerve activity is decreased, increasing the net effect of parasympathetics.
Describe the effect of somatic nerves.
Somatic nerves stimulate striated penile muscles causing greater pressure (ischiocavernosus muscle, bulbospongiosus muscle). Important for ejaculatory force, not maintaining erection
Describe control of emission.
What is emission?
How are smooth muscle cells innervated/what type of receptor?
SYMPATHETIC CONTROL OF EMISSION
Emission – movement of ejaculate into the prostatic/proximal part of urethra
Peristaltic rhythmic contractions via smooth muscle of portions of vas deferens, seminal vesicles, prostate
Direct innervation of smooth muscle cells via alpha adrenergic receptors
Describe the spinal reflex: ejaculation.
What triggers this reflex?
Where do afferents reach spinal cord? What do they trigger?
Contraction of which muscles will propel semen?
Emission “sets the stage” for ejaculation.
Reflex is triggered by entry of semen to bulbous urethra from prostatic urethra. Forceful expulsion of semen.
Spinal cord reflex as well as cerebral control
Afferents reach sacral spinal cord (S2 – S4) triggering efferent somatic motor neurons via pudendal nerve.
Rhythmic contractions of ischiocavernosus and bulbospongiosus muscles – propel semen through the urethra
Note lack of direct voluntary control… autonomic nervous system, then spinal reflex
List the 3 main categories of male reproductive dysfunction and give examples of each. Distinguish between primary, secondary, and tertiary hypogonadism.
PRE-TESTICULAR
TESTICULAR
POST-TESTICULAR
Provide an example of pre-testicular male fertility disorders.
Primary, secondary/tertiary.
PRE-TESTICULAR
Primary Hypergonadotropic hypogonadism (high LH/FSH, low T/DHT)
e.g. Klinefelter syndrome, enzyme deficiencies
Tertiary/Secondary Hypogonadotrpic hypogonadism (low GnRH, low LH/FSH, low T/DHT
e. g. Kallman syndrome, panhypopituitarism,
* hyperprolactinemia (most common)
Provide an example of testicular male fertility disorders.
e.g. Klinefelter syndrome, cryptorchidism, *varicocele (dilated scrotal veins) *most common cause of subfertility in men
Provide an example of post-testicular male fertility disorders.
Ductal obstructions, premature ejaculation, impotence
