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Reproduction Week 1 > Lecture 7: Male Gonadal Physiology > Flashcards

Lecture 7: Male Gonadal Physiology Flashcards

1
Q

What is the significance of GnRH in males?

A

Decapeptide
Derived from pre-pro-GnRH (protein hormone)
24AA signal
Produced in parvi-cellular hypothalamic neurons
Secreted in hypothalamo-hypophyseal portal system

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2
Q

What is halflife of GnRH? Significance?

A

Less than 10 minutes

So serum levels are TOO LOW to detect

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3
Q

What is Kallman’s syndrome?

A

KAL gene mutation
Failure of GnRH neuron precursors to migrate to hypothalamus
Hypogonadotrophic hypogonadism

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4
Q

What is the structure of GnRH receptor on gonadotrophs/LH and FSH receptors?

A

Membrane receptor

GPCR

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5
Q

What are the characteristics GnRH output in men?

A
  1. There is a circadian (diurnal) rhythm
    • 24 hour cycle
    • controlled by melatonin output by the pineal gland
    • greater GnRH action in the early morning
    • highest levels of LH and testosterone
  2. Also a Pulsatile (ultradian) Rhythm
    • pulses every 60-180 minutes
    • higher frequency favors LH secretion
    • lower frequency favors FSH secretion
    • non-physiologic patterns inhibit gonadotropins
      - controlled by sex steroid feedback
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6
Q

At a higher frequency GnRH pulse, what is secreted in men?

A

LH

Same in females

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7
Q

At a lower frequency GnRH pulse, what is secreted in men?

A

FSH

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8
Q

When are the greatest amount of GnRH produced in men?

A

In the early morning

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9
Q

What is the phenomenon of self-priming?

A

When GnRH binding sites increase during troughs of GnRH pulses

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10
Q

What is the flare effect?

A

When excessively frequent of pulsation or continuous GnRH INITIALLY leads to an increase in LH and FSH secretion
After the flare effect, LH and FSH levels become lower

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11
Q

What are the characteristics of LH and FSH?

A

Glycoprotein hormones
Consists of alpha and beta-subunitsgranules
Alpha unit is common but Beta unit confers unique characteristic

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12
Q

What are the characteristics of LH in men?

A 
20 minute half=life 
	-liver enzymes recognize sulfur residues of LH
Pulsatile secretion
Acts on LH receptor on the Leydig Cell
Stimulates synthesis of testosterone
Is inhibited by testosterone
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13
Q

What negatively inhibits LH?

A

‘Testosterone

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14
Q

What are the characteristics of FSH in men?

A 
2 hour half-life
	-sialic acid residues inhibt metabolism
Acts on FSH receptor in Sertoli cell
Stimulates spermatogenesis
Inhibited by Inhibin B
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15
Q

What is the purpose of inhibin B in men?

A

Inhibits FSH production in men

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16
Q

What is the purpose of LH? FSH? IN MEN

A

To promote testosterone production

To promote spermatogenesis

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17
Q

What does estradiol do in men?

A

Modifies GnRH response and decreases LH and FSH pulse amplitude

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18
Q

What is the significance of Inhibin B, Activin and Follistatin system in men?

A

Controls secretion of FSH
Inhibin and follistatin are inhibitory
Activin is stimulatory

19
Q

What structure in testis is responsible for ENDOcrine function?

A

Leydig cell

Steroidogenesis

20
Q

What structure in testis is responsible for EXOcrine function?

A

Sertoli cell
Gametogenesis
Dependent on endocrine function

21
Q

Where do the seminiferous tubules terminate?

A

At the rete testis which anastomose with seminiferous tubules

22
Q

Where are spermatozoa stored?

A

Epididymis

23
Q

In early pregnancy, what do Leydig cells respond to?

A

They respond to hCG to produce testosterone

24
Q

What is the relationship between hCG and Testosterone?

A

In early pregnancy, hCG, rather than LH, is used to bind to Leydig cells to produce testosterone

25
Q

What is the rate limiting step of steroid synthesis?

A 
Steroidogenic Acute Regulatory protein
Transports Cholesterol (initial precursor) across inner mitrochondrial membrane 9which is where pregnenolone is made
26
Q

What are steps of testosterone formation?

A
  1. Steroidogenic Acute Regulatory protein
  2. Cytochrome p450 cc
  3. 3beta hydroxyl steroid dehydrogenase
  4. CYP17 (17 hydroxylase)
  5. 17 beta hydroxyl steroid dehydrogenase
27
Q

What is the mechanism of androgen action?

A

2 zinc-finger DNA binding domains
1st is involved in DNA binding
2nd is involved in dimerization of androgen receptor

28
Q

Difference between Testosterone and LH/FSH?

A

Testosterone = cholesterol/steroid receptor

LH/FSH are peptide hormones so they bind GPCR

29
Q

Where is testosterone in circulation?

A

2% free
44% bound to SHBG (sex hormone binding globulin)
54% bound to albumin

30
Q

What is the difference between spermatogenesis and spermiogenesis?

A 
Seprmatogenesis is characterized by
	Proliferative phase
	-meiotic phse (spermatids)
Spermiogenesiss is characterized by
	-maturation of spermatids to spermatozoa (last part of step)
31
Q

How does sertoli cells support spermatogenesis?

A
  1. create a specialized microenvironment
  2. Expose germ cells (GC) to high levels of testosterone
  3. Coordinate maturation via gap junctions
  4. Transport differentiating GCs towards lumen
32
Q

When do meiosis I and II occur in sperm?

A

Primary spermatocytes = meiosis I

Secondary spermatocytes = meiosis II

33
Q

What are the two types of hypogonadism?

A
  1. primary = testicular failure

2. secondary = dysfunction of hypothalamus or pituitary

34
Q

What are the characteristics of primary hypogonadism?

A
  • infertility precedes androgen deficiency
  • FSH often disproportionately elevated
  • decreasd inhibin B production by Sertoli cell
35
Q

What are the characteristics of hypogonadism?

A

-central defect
-simultaneous infertility and androgen deficiency
Low or normal LH and FSH levels

36
Q

If you have HIGH FSH levels, what kind of hypogonadism do you have?

A

Primary (because gonads are fucked)

37
Q

If you have low/normal FSH levels, what type of hypogonadism is it?

A

Secondary (central defect)

38
Q

How do you diagnose hypogonadism?

A

Infertility

Unequivocally low testosterone

39
Q

What is oligozoospermia?

A

Semen with a low concentration of sperm

40
Q

What is azoospermia?

A

No sperm in semen

41
Q

What are causes of primary hypogonadism?

A
  1. Klinefelter
  2. Cryptorchidism (absence of one or more testes)
  3. testicular torsion
  4. chemotherapy (ketoconazole, cyclophosphamide)
  5. trauma
42
Q

What are causes of secondary hypogonadism?

A

Hypogonadotropic HYPOgonadism
(Kallman’s syndrome)
Suprasellar masses, HIV, pituitary disorders

43
Q

What is TESE?

A

Testicular sperm extraction

Reproduction Week 1 (13 decks)

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