Male Gonad Physiology Flashcards
What does the extrahypothalamic CNS do?
Physical and emotional stress are mediated through this system and acute physical stress decreases testosterone and LH
What parts of the hypothalamus are most important for male fertility?
Preoptic, anterior and ventromedial nuclei
What is GnRH?
A peptide neurohormone that is secreted into the hypothyseal portal system. It has a short half life and its serum levels are too low to detect (since it is in the portal system)
Where is GnRH produced?
Pre-optic anterior hypothalamus
GnRH is released in 2 rhythms, what are they?
- Circadian/diurnal rhythm
- Pulsatile (ultradian) rhythm
- Pulses every 60-
How is the circadian GnRH rhythm controlled
Controlled by melatonin output with greatest release being in the early morning leading to highest levels of LH and testosterone
How often does the pulsatile GnRH rhythm pulse?
Every 60-180minuts
Higher frequency pulses of GnRH favors what?
LH secretion
Lower frequency pulses of GnRH favors what?
FSH secretion
What do non-physiological patterns of pulses do?
Inhibit gonadotropins
What controls the pulsatile rhythm of GnRH secretion?
Sex steroid feedback
What is self-priming?
GnRH binding sites increase during troughs (lower end) of GnRH pulses
What is the flare effect?
Excessively frequent pulsation or continuous GnRH initially increases LH and FSH secretion (flare effect), but leads to GnRH receptor down-regulation w/resulting low LH and FSH levels
What is Leuprolide?
GnRH agonist
Kallmann Syndrome
A disease of hypothalamic dysfunction in which the GnRH neuron precursors fail to migrate to the hypothalamus. Thus, there is a failure to start puberty and a decreased sense of smell.
Pts require LH and FSH supplements
Which hormones have a common alpha subunit?
LH, FSH, hCG, TSH
What confers activity if their alpha subunits are the same?
Unique beta subunit
Are LH and FSH stored in the same secretory granules?
No
What % of the anterior pituitary is gonadotropes?
15%
Is there more LH or FSH in the anterior pituitary?
700 IU LH
200 IU FSH
Describe the metabolism of LH (half life, residues)
Short half life of about 20min (longer than GnRH)
Rapidly metabolized, liver enzymes recognize sulfate residues
What cell type does LH act on and what does it do?
Leydig cells, stimulates the synthesis and release of testosterone
What hormone is responsible for the negative feedback of LH?
Testosterone
Describe the metabolism of FSH (half life, residues)
- Long half life of 2 hours
- Sialic acid residues inhibit metab
- Serum levels remain steady
What cell type does FSH act upon and what does it do?
FSH receptor on Sertoli cells
Stimulates spermatogenesis
What hormone is responsible for the negative feedback of FSH?
Inhibin B acts on the pituitary to inhibit FSH and on the hypothalamus to inhibit GnRH
Describe the testosterone negative feedback mechanism
Testosterone acts on the hypothalamus to decrease GnRH (with downstream LH/FSH effects) AND acts on the pituitary directly to decrease LH
Describe the estradiol negative feedback mechanism
Estradiol acts on the pituitary to decrease LH and FSH (only negative feedback hormone that ONLY acts on pituitary and not the hypothalamus)
Where is estradiol produced and how?
Produced in testicle and adrenal gland. Formed from testosterone which undergoes aromatization in adipose tissue to estrodiol. Very potent.
What does activin do?
It has a stimulatory effect on pituitary FSH
What controls LH and FSH secretion during early fetal development?
Placental hCG controls dev of testes and Wolffian ducts and then pituitary LH takes over as fetal HPG axis matures
What happens with LH and FSH secretion during infancy and childhood?
During this time, hypothalamus is very sensitive to negative feedback so there are very low levels of GnRH, FSH, LH secretion prior to puberty
What happens to LH and FSH secretion during puberty?
Nocturnal FSH and LH pulses begin
HPG axis resets its sensitivity threshold to steroid feedback
Describe DHT’s negative feedback effect
Inhibits hypothalamus secretion of GnRH (only negative feedback hormone that only works on hypothalamus and not pituitary)
What organ is the primary target for LH/FSH?
Testes
What is in the interstitium between seminiferous tubules?
Lymphatics, vessels, Leydig cells
What insulates the testes?
Cremaster muscle
What are the two functions of the testis?
- Endocrine function (steroidogenesis, Leydig cell)
2. Exocrine function (gametogenesis, Sertoli cell)
What are the three structural compartments of the testis?
- Peritubular compartment
- Leydig, basement membrane, ECM, myofibroblasts - Intratubular compartment
- Sertoli and germ cells - Blood-testis barrier
What hormone causes the production of testosterone?
LH! LH binds receptors on Leydig cells causing an increase in cAMP and inc protein synthesis (from cholesterol)
What are the fractions of testosterone in the blood?
2% free, 38% albumin-bound (weakly, so disassociates when necessary, considered usable), 60% SHBG bound
Where does testosterone go in the testis?
Diffuses into seminiferous tubule lumen and binds androgen binding protein (ABP)
What enzyme converts testosterone to DHT?
5-alpha-reductase
What is the rate limiting step of steroid synthesis?
Cholesterol’s transport across the inner mitochondrial membrane via steroidogenic acute regulatory protein
What 4 things do Sertoli cells secrete?
AMH (fetus, inhibits dev of Mullerian ducts), ABP, transferrin, inhibin
What cell type is responsible for the blood-testis barrier?
Sertoli cells
When are Sertoli cells mitotically active/inactive?
Active: puberty
Inactive: adulthood
What hormone stimulates Sertoli cell function throughout life?
FSH
What is the main hormone regulator of spermatogenesis?
Testosterone (which is influenced by FSH)
In what 4 ways do Sertoli cells support spermatogenesis?
- Greate specialized microenvironment
- Expose germ cells to high levels of testosterone
- Coordinate maturation via gap junctions between SC and GCs
- Transport differentiating GCs toward the lumen
Into what cell within the seminiferous tubules does testosterone go?
Enters Sertoli cells bound to ABP. Testosterone concentration here is 100x the peripheral concentration
What is in the basal compartment of the blood-testis-barrier? The adluminal compartment?
Immature germ cells and stem cells (basal)
Germ cells undergoing differentiation and maturation (adluminal)
What are the two phases of spermatogenesis?
Proliferative phase (mitosis) producing primary spermatocytes
Meiotic phase producing early spermatids
What are type Ad spermatogonia?
They line the basal layer and undergo mitosis only to maintain stem cell supply. Remain dormant until puberty.
What are type Ap spermatogonia?
Undergo mitosis to produce clonal population, linked by cytoplasmic bridges, mature simultaneously
What are type B spermatogonia?
Type Ap cells differentiate into type B spermatogonia which enter spermatogenesis
What is spermiogenesis? What 4 things occur?
Maturation process of spermatid to spermatozoa
- Nuclear condensation and programmed repackaging of DNA from histones to protamines
- Acrosome formation
- Residual body separation from sperm (ie xS cytoplasm leaves)
- Tail formation developed form centriole
Where are 60% of sperm stored within the epididymis?
Tail/cauda of epidiymides
How many days does it take for sperm to traverse the epididymis?
12 days
What is the influence of testosterone on the skin?
Hair growth, balding, sebum (oil) producting
What is the influence of testosterone on the liver?
Synthesis of serum proteins
What is the influence of testosterone on the male sexual organs?
Penile growth, spermatogenesis, prostate growth and fxn
What is the influence of testosterone on the brain?
Libido, aggression
What is the influence of testosterone on the muscle?
increase in strength and volume
What is the influence of testosterone on the kidney?
Stimulation of EPO
What is the influence of testosterone on the bone marrow?
Stimulation of stem cells
What is the influence of testosterone on the bone?
Accelerated linear growth closure of epiphyses
What are the symptoms of hypogonadism?
Diminished energy, strength, muscle mass etc….mood changes, poor concentration, memory impairment, reduced motivation etc…
What are the signs of hypogonadism?
Testicular atrophy Gynecomastia Decrease in body hair Infertility Anemia Reduced bone mineral density Changes in body composition (larger)
Primary hypogonadism
- Testicular defect in which infertility precedes testosterone deficiency. FSH is usually disproportionately elevated due to dec inhibin production by sertoli cells
- Can be congenital (klinefelter XXY or Cryptochidism) or acquired (torsion, meds, mumps, radiation, varicocele)
Secondary hypothonadism
- Central defect in which infertility and testosterone deficiency occur simultaneously. Low or inappropriately normal FSH and LH levels
- Can be caused by Kallmann syndrome (no GnRH), pituitary disorders, suprasellar masses, inflammatory diseases, medical illnesses, obesity, meds
