Exam 1 - Male Reproductive Endocrinology Flashcards

1
Q

Besides germ cells (developing sperm), what are the other types of cells in the testis? Describe their location. What are their main functions?

A

Sertoli - within the seminiferous tubules, in between the spermatocytes
- nurse cells that support spermatogenesis

Leydig - in between the seminiferous tubules/intersitial
- produce testosterone

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2
Q

Unlike the ovary, sertoli cells have tight junctions that make up the —- —– ——.

A

blood testis barrier

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3
Q

What stimulates the Leydig cells? What is the overall result?

A
  • LH binds to LH receptors on the Leydig cells
  • androgen biosynthesis - stimulates the conversion of cholesterol into pregnenolone (eventually into testosterone)
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4
Q

What happens to the androgens synthesized by Leydig cells?

A

they diffuse across the Leydig cell membrane into the interstitial spaces, Sertoli cells, and systemic circulation

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5
Q

Describe the biosynthesis pathway of androgens.

A

cholesterol uses LH and cholesterol side-chain cleavage to become pregnenolone

Pregnenolone either becomes progesterone or uses 17a-hydroxylase to become 17 OH Pregnenolone

17 OH Pregnenolone —> DHEA —> Androstenediol or Androstenedione

Progesterone —> (uses 17a-hydroxylase) 17 OH Progesterone —> Androstenedione

Androstenediol and Androstenedione can become Testosterone

Testosterone uses either:
- 5a reductase to become DHT
- Aromatase to become Estradiol

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6
Q

What are the androgens?

A

Testosterone (T) - produced in greatest quantity by the testes, 95% comes from the testis and the other 5% from the adrenal cortex

Less potent than testosterone:

Dehydroepiandrosterone (DHEA)

Androstendione (Andro)

Dihydrotestosterone (DHT)

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7
Q

In general, how are androgens transported? Why?

A

carrier proteins - since steroid hormones are hydrophobic, carrier proteins increase the solubility of steroid hormones and decrease clearance rate

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8
Q

How is testosterone circulated in the bloodstream?

A

60% bound to sex hormone binding globulin (SHBG) produced by the liver

25% bound to albumin produced by the liver

15% unbound (free)
- only free testosterone is biologically active and able to enter the cell to activate receptors

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9
Q

What hormone stimulates the Sertoli cells? What are the effects of this hormone stimulation?

A

FSH binds to FSH receptors on the Sertoli cells

FSH stimulates mitosis of spermatogonia, spermiation (release of sperm into the lumen), produce androgen binding protein (ABP), and synthesize/secrete inhibin

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10
Q

What is inhibin?

A

member of TGFBeta hormone family, inhibits AP from secreting FSH (but not LH)

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11
Q

What does androgen binding protein (ABP) do?

A

maintain high testosterone levels in the seminiferous tubule (200x greater here than in general circulation) near the developing germ cells

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12
Q

What is the different between ABP and SHBG?

A

same amino acid sequence, but ABP is produced by the testes and the two cannot cross the blood testis barrier (so they stay in their respective locations)

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13
Q

Besides the effects of FSH, what else do the Sertoli cells do?

A

maintain the blood testis barrier - form the tight junctions between cells that create an immune barrier

phagocytize abnormal sperm and excess cytoplasm

secrete fluid that nourishes sperm/provides transport medium

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14
Q

Describe the association between Leydig and Sertoli cells. What do each of them produce when stimulated by a AP hormone, and what crosses between the cells?

A

Leydig cells:
LH activates cAMP, protein kinases, which convert cholesterol to pregnenolone and eventually testosterone. Testosterone diffuses out (into the extracellular space) and across to the Sertoli cells.

Sertoli cells:
FSH activates cAMP which supports spermiation, mitosis of spermatogonia, creation of inhibin, and creation of ABP. ABP binds the testosterone from the Leydig cells, trapping it in the Sertoli cells.

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15
Q

What is the difference in testosterone concentration inside the seminiferous tubule vs. in the systemic circulation/extracellular fluid? Why?

A

200x higher in the tubule due to ABP production which traps it inside (ABP cant cross/move out)

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16
Q

Most testosterone in the sytemic circulation is carried by…
which allows…

A

SHBG
more testosterone to remain in the blood that would if it was all free

17
Q

What mechanism occurs when testosterone enters a cell (like skeletal muscle or hair follicle)? What is the result?

A

testosterone either remains as testosterone or is turned into DHT by 5a-reductase

Both of them bind to a receptor and form a hormone-receptor complex

hormone-receptor complex acts as a transcription factor to modulate the rate of transcription of steroid hormone-responsive genes

this either induces or represses gene transcription to produce a desired cellular response

18
Q

What are the 3 general types of effects of testosterone can have in adults?

A

reproductive, anabolic, and androgenic

19
Q

What are the reproductive effects of testosterone in adults?

A

maintenance of internal reproductive tract

required for spermatogenesis (must be 200x higher in tubule)

20
Q

What form of testosterone produces anabolic effects?
What are the anabolic effects?

A

testosterone

increased skeletal muscle mass and increased red blood cell production

21
Q

What form of testosterone produces androgenic effects?
What are the androgenic effects?

A

DHT

increased libido
sebum formation by the sebaceous glands (acne)
facial hair growth
male-pattern baldness (androgenic alopecia in those who are genetically predisposed)

22
Q

What type of feedback does inhibin have, and on what tissue?

A

negative feedback to the anterior pituitary for FSH production (increase inhibin, decrease FSH)

23
Q

What types of feedback do the androgens have, and on what tissues?

A

negative feedback to the anterior pituitary for production of LH and FSH

negative feedback to the hypothalamus via KiSS peptin neurons for production of GnRH

24
Q

Describe how KiSS1 neurons stimulate the adult reproductive axis.

A

Kiss1 neurons express androgen receptors

Androgens bind and regulate KiSS expression (less androgens = more KiSS expression)

Receptors for kisspeptin are on the GnRH neurons

KiSS stimulation triggers the release of GnRH, which stimulates the pituitary to release LH and FSH

less androgens –> kiss stimulation –> GnRH release –> more FSH and LH –> more androgens

25
Q

What is endogenous vs exogenous? Can the body tell the difference regarding testosterone? What impact does this have?

A

endogenous - produced by the body
exogenous - made outside the body

The body cannot tell the difference

Exogenous testosterone still gives negative feedback to the anterior pituitary, and therefore will reduce the release of LH and FSH which overall decreases the amount of testosterone in the Sertoli cells/decreases sperm production

26
Q

In the male hormonal contraception study, what were the 4 general conclusions about taking exogenous testosterone?

A
  • increases serum testosterone (the amount bound and free)
  • suppresses LH and FSH
  • sperm concentration decreased 10-20x (from 100 million/mL to 5-10 million/mL) to a level below infertility
  • sperm production took 6-12 weeks to be suppressed and to recover
27
Q

What are the three types of sexual dimorphism?

A

genetic sex (XX or XY)
gonadal sex (testes or ovaries)
phenotypic sex (male or female)

28
Q

Fetal development of the internal reproductive tract is directly affected by…

A

testosterone

29
Q

The internal female reproductive tract develops from the…

A

Mullerian ducts

30
Q

The internal male reproductive tract develops from the…

A

Wolffian ducts

31
Q

Fetal development of the male external genitalia and prostate depends on…

A

the conversion of testosterone to DHT via 5a-reductase in target tissues

32
Q

What triggers the conversion of gonads into testes? When does this occur in fetal development?

A

SRY (the sex determining region on the Y chromosome)

6-7 weeks

33
Q

What do SRY gene products contribute to?

A

differentiation of gonads into testes

production of Anti-Mullerian Hormone (AMH/MIF) by the Sertoli cells

production of testosterone by Leydig cells

34
Q

What two things happen once the gonads differentiate into testes? When do these things occur in fetal development?

A

production of testosterone (8-9 weeks)

production of Mullerian Inhibiting Factor/Anti-Mullerian Hormone (6-8 weeks)

35
Q

What does the production of Anti-Mullerian Hormone cause? When does that occur in fetal development?

A

the mullerian ducts regress (7-10 weeks)

36
Q

What does the production of testosterone cause?When does that occur in fetal development?

A

testosterone - wolffian ducts to male reproductive tracts/internal genitalia (9-12 weeks)

5a-reductase converts T to DHT - genitalia to male genetalia/external genitalia (9-13 weeks)

37
Q

Overall, differentiation into male genitalia is regulated by —— and —–

A

testosterone and DHT (requires 5a-reductase)

38
Q

What is 5a-reductase deficiency? What are the results?

A

deficiency of the enzyme (5a-reductase) required for conversion of testosterone to DHT, which is required for fetal development of external genitalia and prostate

results in normal internal genitalia (differentiation of testes only requires SRY and internal system only needs testosterone)

incomplete masculinization of the external genitalia (because that requires DHT which needs 5a-reductase)

increased testosterone production at puberty results in masculanization

39
Q

What is androgen insensitivity? What are the results?

A

deficiency in androgen receptors on target cells (defect in the gene controlling expression of androgen receptors, affects the actions of T and DHT)

gonads become testes and the Sertoli cells make AMH - no testosterone or DHT involved yet

but, T and DHT are needed for external genitalia formation and masculanization. Since there are no receptors, this results in the female phenotype (genitals and external appearance)

testosterone levels can be normal

patients may present with primary amennorrhea in their late teens