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SHP - Pharmacology & Therapeutics > The Gonads; Sexual differentiation, Development & Hormones > Flashcards

The Gonads; Sexual differentiation, Development & Hormones Flashcards

1
Q

Name the respective gonads and what they do.

A

Testis (males)
Ovaries (females)

Gonads (pair) are reproductive glands that maintain a species; producing gametes (cells that contain genetic information that is transferred) and providing sex hormones.

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2
Q

What is the function of the reproductive tract?

A
  • Provides passage and supportive secretions for gametes (enabling cells to be delivered and fertilise/be fertilised)
  • Consists of ducts and associated glands
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3
Q

What cells do the male foetal gonads comprise of?

A

Primordial germ cell: Spermatozoa

Mesenchymal tissue: Sertoli and Leydig cells

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4
Q

What cells do the female foetal gonads comprise of?

A

Primordial germ cell: Oocytes

Mesenchymal tissue: Granulosa and Theca cells

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5
Q

What are primordial germ cells responsible of?

A

Produces gamete and carries genetic information (spermatozoa/oocytes)

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6
Q

What is mesenchymal tissue and the two main different functions associated?

A
  • Forms the matrix of the gonads surrounding the primordial germ cell
  • Sertoli (male) and granulosa (female) cells nurse/foster germ cells during maturation and movement into the genital duct system, whilst also producing oestrogens and androgen binding protein (ABP)
  • Leydig (male) and theca (female) cells produce androgenic hormones
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7
Q

Describe the genetic basis of sexual differentiation.

A
  • Parents have 46 chromosomes (22 paired autosomes; 23rd is sex chromosome (XY - male, XX - female) (diploid)
  • Meiotic cell division leads to formation of ovum or spermatozoa possessing 23 chromosomes - primordial germ cell formation (haploid)
  • Fertilisation of ovum with ‘Y’ spermatozoa yields male, fertilisation with ‘X’ yields female (Y is more important determinant of ‘maleness’ but X also contributes)
  • Embryro develops via mitotic cell division, with each cell containing 46 chromosomes (23 pairs) (diploid)
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8
Q

Describe the stages of the development of male foetal gonads and genitalia.

A

Weeks 3 - 7: both Wolffian and Mullerian genital duct develop either side of gonads; embryo is sexuallly indeterminate at this point
Week 7:
- Anti-Mullerian hormone (AMH; Sertoli cells) cause atrophy of Mullerian duct and initiates descent of testes
- FSH production terminates action of AMH
Week 9: Testosterone (Leydig cells) stimulates Wolffian duct to differentiate into epididymis, vas deferens, seminal vesicles and ejaculatory duct.

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9
Q

What is the main difference regarding the development of male foetal gonads/genitalia rather than female?

A

Positive hormone influence (testosterone from leydig cells) is required to produce a masculine format.

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10
Q

What is noteworthy regarding Weeks 3 to 7 of foetal gonad/genitalia development?

A
  • Genetically sex has already been determined but cannot distinguish distinguish physically at this point which sex it is
  • Sexual differentiation is not dependent upon fetal pituitary gonadotropins (not LH/FSH, but androgen dependent (testosterone/AMH)
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11
Q

Describe the stages of the development of female foetal gonads and genitalia.

A

Weeks 3 - 7: Both Wolffian and Mullerian genital ducts develop either side of gonads (embryo is sexually indeterminate)
Weeks 10 - 11:
- Absence of testosterone leads to regression of Wolffian duct
- Absence of AMH (anti-Mullerian hormone) leads to growth and differentiation of Mullerian Duct into fallopian tubes, uterus, cervix, and vagina
Weeks 18-20:
- Process completed; development of female genitalia does not require gonad hormones

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12
Q

What determines the gonadotropin pattern secretion and how does it differ between males and females?

A
  • Determined by testosterone; constant = males, cyclical = females (pre-set neural wiring)
  • Once female pattern is established, testosterone cannot influence organs
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13
Q

What enzyme is testosterone converted into once secreted into circulation and what is the product called?

A
  • Intracellular 5-alpha-reductase

- Testosterone is converted to dihydrotestosterone

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14
Q

What components of the external male sex organ develop as a result of testosterone?

A
  • Glans penis
  • Scrotum
  • Penile urethra
  • Prostate glands
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15
Q

What may a genetic abnormality in the enzyme intracellular 5-alpha-reductase result in?

A
  • Intracellular 5-alpha-reductase is responsible for conversion of testosterone to dihydrotestosterone
  • Genetic abnormality in enzyme may mean poorly developed penis/prostate/testes
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16
Q

Are any hormones responsible for the development of the female external sex organs?

A
  • No overt hormonal influence

- Lower vagina, clitoris, labia majora, labia minora

17
Q

How does exposure to high levels of androgens affect external female sex organs after differentiation?

A

It causes an enlargement of the clitoris (due to its relation to the glans penis)

18
Q

What are the hormones LH/FSH and how do they differ?

A
  • Gonadotropins from the anterior pituitary
  • Luteinizing Hormone (LH) = 28,000 dalton glycoprotein
  • Follicle Stimulating Hormone = 33,000 dalton glycoprotein
    (they are large glycoproteins)
  • Consist of identical α subunit (14,000 dalton) but differing β subunits
19
Q

How do the subunits of LH/FSH work together?

A
  • Physiological activity lies in the β subunit

- But is inactive with the α subunit

20
Q

What do gonadotropins do?

A
  • Produce steroidogenesis via plasma membrane receptors (unlike steroid hormones; intracellular receptors), bringing about changes in cAMP and activation of protein kinase C (second messenger signalling)
21
Q

Where are LH receptors found and what occurs upon activation?

A
  • Present on Leydig (male) and theca (Female) cells (of mesenchymal tissue)
  • LH increases uptake of HDL and LDL
  • LH activates 20, 22 desmolase enzyme (CYP11A1)
  • Activates granulosa cells (other cell type in mesenchymal tissue) to produce progesterone
22
Q

What is the enzyme CYP11A1 (20, 22 desmolase enzyme) responsible for and how is it activated?

A
  • Converts cholesterol to pregnanolone, and then to androsterone
  • Activated by LH
23
Q

What enzyme is responsible for the conversion of testosterone to estradiol?

A

Aromatase enzyme (CYP17)

24
Q

What does FSH activation do?

A
  • Activates ovarian granulosa cells and leydig cell aromatase enzyme (CYP17; converting androsterone previously made from cholesterol in leydig/theca cells to testosterone to estradiol)
25
Q

How do gonadotropins have a synergistic effect on one another?

A
  • Activation of FSH receptors increases LH expression; cells (leydig in males/theca in females, granulosa too) become sensitised to LH; increasing LH activity
  • Supply of androsterone from interstitial (leydig/theca) cells for oestrogen formation; paracrine communication/transport
  • Production of progesterone from granulosa cells
    »> Net outcome; increased oestrogen production
26
Q

How does the hypothalamus play a role in regulating anterior pituitary gonadotropins?

A
  • Neurones terminate on portal vessels of the Median Eminence and secreted GnRH (LHRH)
  • GnRH is a decapeptide (much smaller than anterior pituitary hormones) which is released phasically by neurones
  • Frequency of release determines action; fast release of GnRH brings about different response than slow release of GnRH
27
Q

How do oestradiol and testosterone regulate the anterior pituitary hormones?

A
  • Exert negative feedback control on anterior pituitary/hypothalamus
28
Q

What estrogens are there?

A
  • Progesterone

- Testosterone

29
Q

How do the estrogens progesterone and testosterone reach their target and act?

A
  • V. lipophilic molecules
  • Estradiol (made from conversion of progesterone or testosterone respectively) binds with intracellular receptor
  • Brings about interaction between CoA (coactivator protein) and estradiol receptor (oestrogen response element) stimulating transcription
  • Response is slow in onset due to modulating gene transcription
  • Some cell surface receptors also present for faster response
30
Q

How does the antagonist clomiphene work?

A
  • Promotes interaction between CoR (corepressor protein) and estradiol receptor instead of CoA (coactivator) in the nucleus
  • Altering (reducing) protein transcription, leading to reduced oestrogen/inhibition

SHP - Pharmacology & Therapeutics (2 decks)

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