Lecture 5 Endocrine Regulation of Male Reproduction 1

Question 1

Which hormone is the central regulator of reproduction?

Answer 1

GnRH

Question 2

How is GnRH secretion maintained tonic?

Answer 2

Higher control creates inhibitory effect by GABA which establishes GnRH pulse generator.
Negative feedback on GnRH by the testosterone produced from Leydig cells. Pulsatile release can also be maintained by oestrogen (since testosterone is converted to oestrogen by aromatase and has a negative feedback effect)

Question 3

Outline the hypothalamo-pituitary-testicular axis.

Answer 3

GnRH released from the hypothalamus, causes release of FSH and LH from gonadotropic cells. FSH stimulates Sertoli cell differentiation, and causes release of inhibin from Sertoli cells to create negative feedback on gonadotropic cells. LH stimulates Leydig cell differentiation and release of testosterone which has a negative feedback on GnRH.

Question 4

What are the higher controls of GnRH

Answer 4

Prolactin: increases GABA, suppress GnRH e.g. baby at breast (natural contraceptive)
Corticotropin releasing factor CRF: stress, increases CRF from brain, increases GABA, suppresses GnRH

Question 5

Are there testosterone and oestrogen receptors on the GnRH releasing cells?

Answer 5

No, that is way testosterone and oestrogen have an inhibitory effect on GnRH via kisspeptin

Question 6

What are the functions of kisspeptin?

Answer 6

Mediates onset of puberty, as there is upregulation of hypothalamic KISS1 and its receptor at puberty.
Establishes negative feedback loop between testosterone and oestrogen (they are antagonists to KISS so suppress GnRH)

Question 7

What is the starting compound of all steroidogenesis processes (aldoserone, cortisol, oestrogen, testosterone)

Answer 7

Cholesterol

Question 8

What is the enzyme responsible for the conversion of progesterone to androgens?

Answer 8

17, 20 lyase

Question 9

How are oestrogens made?

Answer 9

Cholesterol - progesterone - androgen - oestrogens by aromatase

Question 10

What is the converting enzyme for testosterone to DHT

Answer 10

5a-reductase

Question 11

Outline testosterone synthesis.

Answer 11

Occurs in Leydig cells. LH binds to its receptor on Leydig cells, causes ATP to convert to cAMP, this activates PKA to phosphorylase StAR. StAR is a transporter that moves cholesterol into the mitochondria of the Leydig cell. The cholesterol is then converted to pregnenolone by SCC which moves out of the mitochondria. Pregnenolone then converted to testosterone.

Question 12

What is hypogonadism and how does it occur?

Answer 12

Hypogonadism is deficiency in androgen secretion and/or sperm production.
It may be due to 1) testicular (primary Leydig cell dysfunction) or 2) Hypothalamic-pituitary (secondary Leydig cell dysfunction)

Question 13

Name the 3 stages of spermiogenesis

Answer 13

Spermatocytogenesis (mitotic proliferation or clonal expansion)
Meiotic dividison (reduction)
Spermiogenesis (germ cell remodelling)

Question 14

What occurs during spermatocytogenesis and where?

Answer 14

Spermatogonia undergo 6 mitotic divisions. At basal seminiferous tubules, between Sertoli cells

Question 15

What occurs during meiosis stage of spermiogenesis?

Answer 15

Move from basal to luminal region of seminiferous tubule via the blood-testis barrier to avoid immune cells as genetic reduction occurs 2n -> n. Genetic recombination also occurs during telophase, mixing of maternal and paternal chromosome regions.

Question 16

What occurs during spermiogenesis?

Answer 16

Migration of Golgi and centrioles to apical pole. Acrosome cap and flagellum forms. Golgi moves away from nucleus, nuclear condensation and shaping, elongation of spermatid. Spermiation (release of sperm into lumen of seminiferous tubule).

Question 17

Is the early or late stage of spermatogenesis sensitive to testosterone?

Answer 17

Late meiotic and spermiogenesis. So SCAR-KO (Sertoli cell androgen receptor KO) would mean no spermatids

Question 18

Is the early or late stage of spermatogenesis sensitive to FSH?

Answer 18

Spermatocytogenesis and early meiosis. So FSHr-KO would mean reduced spermatogenesis

Question 19

What would be seen with FSHr-KO and SCAr-KO (Sertoli cell androgen receptor)?

Answer 19

Germ cell reduction. Weight of testis reduced.

Question 20

What is the ‘Hayflickness’ theory of cells?

Answer 20

Cells have replicative senescence, meaning they have finite number of cell divisions possible.

Question 21

How do cells ‘age’?

Answer 21

Gradual decline in performance of organ systems. Increased cell turnover, altered gene expressions.

Question 22

How germ cells remain immortal?

Answer 22

No senescence because germ cells express telomerase which extends telomere repeats so no shortening with every division.