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Reproduction > Male Gonad Physiology > Flashcards

Male Gonad Physiology Flashcards

1
Q

What does the extrahypothalamic CNS do?

A

Physical and emotional stress are mediated through this system and acute physical stress decreases testosterone and LH

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2
Q

What parts of the hypothalamus are most important for male fertility?

A

Preoptic, anterior and ventromedial nuclei

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3
Q

What is GnRH?

A

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)

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4
Q

Where is GnRH produced?

A

Pre-optic anterior hypothalamus

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5
Q

GnRH is released in 2 rhythms, what are they?

A
  1. Circadian/diurnal rhythm
  2. Pulsatile (ultradian) rhythm
    - Pulses every 60-
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6
Q

How is the circadian GnRH rhythm controlled

A

Controlled by melatonin output with greatest release being in the early morning leading to highest levels of LH and testosterone

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7
Q

How often does the pulsatile GnRH rhythm pulse?

A

Every 60-180minuts

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8
Q

Higher frequency pulses of GnRH favors what?

A

LH secretion

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9
Q

Lower frequency pulses of GnRH favors what?

A

FSH secretion

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10
Q

What do non-physiological patterns of pulses do?

A

Inhibit gonadotropins

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11
Q

What controls the pulsatile rhythm of GnRH secretion?

A

Sex steroid feedback

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12
Q

What is self-priming?

A

GnRH binding sites increase during troughs (lower end) of GnRH pulses

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13
Q

What is the flare effect?

A

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

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14
Q

What is Leuprolide?

A

GnRH agonist

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15
Q

Kallmann Syndrome

A

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

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16
Q

Which hormones have a common alpha subunit?

A

LH, FSH, hCG, TSH

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17
Q

What confers activity if their alpha subunits are the same?

A

Unique beta subunit

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18
Q

Are LH and FSH stored in the same secretory granules?

A

No

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19
Q

What % of the anterior pituitary is gonadotropes?

A

15%

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20
Q

Is there more LH or FSH in the anterior pituitary?

A

700 IU LH

200 IU FSH

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21
Q

Describe the metabolism of LH (half life, residues)

A

Short half life of about 20min (longer than GnRH)

Rapidly metabolized, liver enzymes recognize sulfate residues

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22
Q

What cell type does LH act on and what does it do?

A

Leydig cells, stimulates the synthesis and release of testosterone

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23
Q

What hormone is responsible for the negative feedback of LH?

A

Testosterone

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24
Q

Describe the metabolism of FSH (half life, residues)

A
  • Long half life of 2 hours
  • Sialic acid residues inhibit metab
  • Serum levels remain steady
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25
Q

What cell type does FSH act upon and what does it do?

A

FSH receptor on Sertoli cells

Stimulates spermatogenesis

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26
Q

What hormone is responsible for the negative feedback of FSH?

A

Inhibin B acts on the pituitary to inhibit FSH and on the hypothalamus to inhibit GnRH

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27
Q

Describe the testosterone negative feedback mechanism

A

Testosterone acts on the hypothalamus to decrease GnRH (with downstream LH/FSH effects) AND acts on the pituitary directly to decrease LH

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28
Q

Describe the estradiol negative feedback mechanism

A

Estradiol acts on the pituitary to decrease LH and FSH (only negative feedback hormone that ONLY acts on pituitary and not the hypothalamus)

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29
Q

Where is estradiol produced and how?

A

Produced in testicle and adrenal gland. Formed from testosterone which undergoes aromatization in adipose tissue to estrodiol. Very potent.

30
Q

What does activin do?

A

It has a stimulatory effect on pituitary FSH

31
Q

What controls LH and FSH secretion during early fetal development?

A

Placental hCG controls dev of testes and Wolffian ducts and then pituitary LH takes over as fetal HPG axis matures

32
Q

What happens with LH and FSH secretion during infancy and childhood?

A

During this time, hypothalamus is very sensitive to negative feedback so there are very low levels of GnRH, FSH, LH secretion prior to puberty

33
Q

What happens to LH and FSH secretion during puberty?

A

Nocturnal FSH and LH pulses begin

HPG axis resets its sensitivity threshold to steroid feedback

34
Q

Describe DHT’s negative feedback effect

A

Inhibits hypothalamus secretion of GnRH (only negative feedback hormone that only works on hypothalamus and not pituitary)

35
Q

What organ is the primary target for LH/FSH?

A

Testes

36
Q

What is in the interstitium between seminiferous tubules?

A

Lymphatics, vessels, Leydig cells

37
Q

What insulates the testes?

A

Cremaster muscle

38
Q

What are the two functions of the testis?

A
  1. Endocrine function (steroidogenesis, Leydig cell)

2. Exocrine function (gametogenesis, Sertoli cell)

39
Q

What are the three structural compartments of the testis?

A
  1. Peritubular compartment
    - Leydig, basement membrane, ECM, myofibroblasts
  2. Intratubular compartment
    - Sertoli and germ cells
  3. Blood-testis barrier
40
Q

What hormone causes the production of testosterone?

A

LH! LH binds receptors on Leydig cells causing an increase in cAMP and inc protein synthesis (from cholesterol)

41
Q

What are the fractions of testosterone in the blood?

A

2% free, 38% albumin-bound (weakly, so disassociates when necessary, considered usable), 60% SHBG bound

42
Q

Where does testosterone go in the testis?

A

Diffuses into seminiferous tubule lumen and binds androgen binding protein (ABP)

43
Q

What enzyme converts testosterone to DHT?

A

5-alpha-reductase

44
Q

What is the rate limiting step of steroid synthesis?

A

Cholesterol’s transport across the inner mitochondrial membrane via steroidogenic acute regulatory protein

45
Q

What 4 things do Sertoli cells secrete?

A

AMH (fetus, inhibits dev of Mullerian ducts), ABP, transferrin, inhibin

46
Q

What cell type is responsible for the blood-testis barrier?

A

Sertoli cells

47
Q

When are Sertoli cells mitotically active/inactive?

A

Active: puberty

Inactive: adulthood

48
Q

What hormone stimulates Sertoli cell function throughout life?

A

FSH

49
Q

What is the main hormone regulator of spermatogenesis?

A

Testosterone (which is influenced by FSH)

50
Q

In what 4 ways do Sertoli cells support spermatogenesis?

A
  1. Greate specialized microenvironment
  2. Expose germ cells to high levels of testosterone
  3. Coordinate maturation via gap junctions between SC and GCs
  4. Transport differentiating GCs toward the lumen
51
Q

Into what cell within the seminiferous tubules does testosterone go?

A

Enters Sertoli cells bound to ABP. Testosterone concentration here is 100x the peripheral concentration

52
Q

What is in the basal compartment of the blood-testis-barrier? The adluminal compartment?

A

Immature germ cells and stem cells (basal)

Germ cells undergoing differentiation and maturation (adluminal)

53
Q

What are the two phases of spermatogenesis?

A

Proliferative phase (mitosis) producing primary spermatocytes

Meiotic phase producing early spermatids

54
Q

What are type Ad spermatogonia?

A

They line the basal layer and undergo mitosis only to maintain stem cell supply. Remain dormant until puberty.

55
Q

What are type Ap spermatogonia?

A

Undergo mitosis to produce clonal population, linked by cytoplasmic bridges, mature simultaneously

56
Q

What are type B spermatogonia?

A

Type Ap cells differentiate into type B spermatogonia which enter spermatogenesis

57
Q

What is spermiogenesis? What 4 things occur?

A

Maturation process of spermatid to spermatozoa

  1. Nuclear condensation and programmed repackaging of DNA from histones to protamines
  2. Acrosome formation
  3. Residual body separation from sperm (ie xS cytoplasm leaves)
  4. Tail formation developed form centriole
58
Q

Where are 60% of sperm stored within the epididymis?

A

Tail/cauda of epidiymides

59
Q

How many days does it take for sperm to traverse the epididymis?

A

12 days

60
Q

What is the influence of testosterone on the skin?

A

Hair growth, balding, sebum (oil) producting

61
Q

What is the influence of testosterone on the liver?

A

Synthesis of serum proteins

62
Q

What is the influence of testosterone on the male sexual organs?

A

Penile growth, spermatogenesis, prostate growth and fxn

63
Q

What is the influence of testosterone on the brain?

A

Libido, aggression

64
Q

What is the influence of testosterone on the muscle?

A

increase in strength and volume

65
Q

What is the influence of testosterone on the kidney?

A

Stimulation of EPO

66
Q

What is the influence of testosterone on the bone marrow?

A

Stimulation of stem cells

67
Q

What is the influence of testosterone on the bone?

A

Accelerated linear growth closure of epiphyses

68
Q

What are the symptoms of hypogonadism?

A

Diminished energy, strength, muscle mass etc….mood changes, poor concentration, memory impairment, reduced motivation etc…

69
Q

What are the signs of hypogonadism?

A 
Testicular atrophy
Gynecomastia
Decrease in body hair
Infertility
Anemia
Reduced bone mineral density
Changes in body composition (larger)
70
Q

Primary hypogonadism

A
  • 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)
71
Q

Secondary hypothonadism

A
  • 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

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