Lecture 2 Flashcards

1
Q

What are the gonads and their 2 main functions?

A

Gonads are primary reproductive organs, they are the pair of testes in males and pair of ovaries in females

2 functions:

  1. Producing gametes (spermatogenesis gives rise to sperm in males and oogenesis gives rise to ova or egg in females)
  2. Production of sex hormones (testosterone in males and estrogen/progesterone in females
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2
Q

What does the prostate gland do?

What do the seminiferous tubules do?

A

Prostate gland secreted a slightly acidic milky fluid that makes up 50-75% volume of semen
Although the prostate secretion is acidic, semen is alkalinic due to fluid from seminal vesicle (seminal alkalinity neutralizes vaginal acidity)

The seminiferous tubule is an epithelium forked by Sertoli cells
The most immature germ cells (spermatogonia) are near the periphery of the tubule, whereas the mature germ cells (spermatozoa) are near the lumen of the tubule

Slide 2

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3
Q

What are the steps of spermatogenesis?

A

Primordial germ cells migrate to gonads (become spermatogonia)
At onset of puberty, spermatogonia undergo repeated mitotic division
Some spermatogonia undergo first meiotic division, making them spermatocytes
At prophase, each spermatocyte has full complement of duplicated chromosomes, each primary spermatocyte divides into 2 secondary spermatocytes
Secondary spermatocyte enters second meiotic division making 2 spermatids

Slide 3

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4
Q

What is the hypothalamus-pituitary axis?

It’s 3 major functions?

A

Hypothalamus produces neurohormones called hypothalamic releasing hormones (these stimulate or inhibit release of pituitary hormones)

Functions:

  1. Secretion of regulatory hormones to control activity of anterior lobe of pituitary gland
  2. Production of ADH and oxytocin
  3. Control of sympathetic output to adrenal medulla

Slide 4

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5
Q

What are the 6 peptide hormones that the anterior pituitary secretes?

What are the 2 hormones the posterior pituitary secretes?

A

Glandular tissue in anterior pituitary synthesizes and secretes GH (growth hormone), TSH, ACTH, FSH (follicle-stim hormone), LH (luteinizing hormone), and PRL

Pareventricular nucleus of hypothalamus synthesizes AVP (arginine vasopressin) and OT (oxytocin) and these are secreted by posterior pituitary
Posterior pituitary regulates water balance and uterine contraction

Slide 5-6

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6
Q

What is the male hypothalamic pituitary axis?

2 functions

A
  1. Production of male gametes (spermatogenesis) in seminiferous tubules
  2. Androgen biosynthesis in leydig cells of the testes

Hypothalamus produces GnRH which stims gonadotrophs in ant. pituitary to secrete 2 gonadotrophins, LH, and FSH
Neurons that synthesize and release GnRH are primarily located in arcuate nucleus and preoptic area

Slide 8-9

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7
Q

Where do LH and FSH go after being stimmed by GnRH and released by gonadotrophs?

A

LH binds to receptors on leydig cells and stims transcription of proteins involved in biosynthesis of testosterone (LH and hCG are very similar)

FSH binds to receptors on the basolateral membrane of Sertoli cells, stimulating gene transcription and protein synthesis

These two are made of α and β subunits, the alphas are identical while the betas differ

Slide 10-11

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8
Q

What is luteinizing hormone (LH)?

A

In both sexes LH stims secretion of sex steroids from the gonads (in males they bind to leydig and females they bind to theca cells in ovary)
Secretes testerone in both but in females the granulosa cells convert to estrogen
Binds to G coupled protein receptor on cell, stims adenylyl cyclase, form cAMP, activates PKA, makes testosterone

Stimulates luteal function in female (how it gets name)

LH also stims SCP and SCP-2

Slides 12-13

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9
Q

What is follicle stimulating hormone (FSH)?

A

FSH binds to G protein coupled receptor, stims adenylyl cyclase, increase [cAMP]i, activate PKA, transcripts certain genes, increase protein synthesis
Proteins synthesized by this:
Androgen-binding protein (ABP)- keeps testosterone levels high
P450 aromatase- converts testosterone to estrogen
Growth factors- increase spermatogonia, spermatocytes, spermatids in testis
Inhibins- paracrine and endocrine actions, feedback role in hypothalamus-pituitary axis

Slides 14-15

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10
Q

How do Sertoli and leydig cells cross talk?

A

Sertoli cells convert testosterone-synthesized by leydig cells to estrogen, which acts on leydig cells
FSH acts on Sertoli cells to produce growth factors that may increase the number of LH receptors on leydig cells

Slide 18-19

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11
Q

What are the conditions necessary for optimal spermatogenesis?

A

Leydig and Sertoli cells, 2 gonadotrophins (LH and FSH), and one androgen (testosterone) are require for optimal conditions

LH or hCG are used in oligospermic men for spermatogenesis

Slide 20

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12
Q

What are the plasma levels of FSH, LH, and testosterone from puberty to adulthood?

A

During early puberty in boys, both FSH and LH increase while the leydig cells proliferate and plasma levels of testosterone increase
FSH production is greater than that of LH during the prepubertal period, this is reversed after puberty
Preferential release of LH May reflect maturation of the testes, which secrete inhibin, which inhibits FSH

Slide 21

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13
Q

How is testosterone synthesized?

A

Leydig cells use a series of 5 enzymes to convert cholesterol to testosterone
Behind in mitochondria, cytochrome P450 side chain cleavage (SCC) removes long chain
In smooth ER, 17α-hydroxylase adds hydroxyl group
In SER, 17, 20-desmolase removes side chain from carbon 17
Testis can also use 5α reductase to convert testosterone to dihydrotestosterone

Slide 23-24

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14
Q

What are the 5 steroid hormone receptors?

A
  1. Glucocorticoid receptor (GR)
  2. Mineralocorticoid receptor (MR)
  3. Progesterone receptor (PR)
  4. Estrogen receptor (ER)
  5. Androgen receptor (AR)
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15
Q

What is the androgen receptor?

A

Androgens diffuse into target cells and act by binding to androgen receptors (present in genital tissues)
Androgen receptor functions as a homodimer (AR/AR)

Slide 26

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16
Q

What is the mechanism of action of testosterone and other steroids?

A

Steroid hormones bind to intracellular receptors that regulate gene transcription
Activated steroid hormone binds to specific stretches of DNA called hormone response elements or steroid response elements (SREs)

Small fraction (2%) of testosterone circles around free, enters cells by passive diffusion and exerts biological actions

Once in a cell, testosterone either binds to high affinity androgen receptor it gets converted to DHT

Slide 27-28

17
Q

What is dihydrotestosterone?

A

Cytoplasmic 5α-reductase converts testosterone to dihydrotestosterone (DHT) which binds to same androgen receptor as testosterone but with an affinity 100-fold higher than testosterone

18
Q

What happens with testosterone in the aging male?

A

Men experience a casual decline in serum testosterone levels with age

LH does not decrease when testosterone does

Slide 30-31

19
Q

What is the metabolism of testosterone?

A

Testosterone is mainly metabolized in the liver and prostate
Only small amounts get into urine without metabolism

Testosterone converted to 17-ketosteroids in the liver and converted to DHT in prostate

20
Q

What are the functions of androgens?

A

They trigger conversion of the wolffian ducts to the male ejaculatory system
They direct the differentiation of the urogenital sinus and external genitalia

They also determine male secondary sexual characteristics:

  • development of external and internal genitalia depends on this
  • they stimulate adult maturation of external genitalia and accessory sex organs (penis, scrotum, prostate, seminal vesicle
  • also determine male secondary sex characteristics (deepening of voice
  • muscle development and growth

Slides 33-35

21
Q

What is feminization syndrome?

A

Testicular descent is an androgen dependant process
Development of structures involved in testicular descent is dependant on testosterone

Testes fail to descent in testosterone-deficient states caused by inadequate secretion
5α-reductase deficiency

Slides 36-38

22
Q

What is male pseudohermaphroditism?

A

Any defect in the mechanisms by which androgens act on target tissues in genotypic makes
Affected individuals have a normal karyotype (46, XY) and unambiguous and clearly distinct male gonads, but ambiguous external genitalia or may appear as females

Slides 39-40