Physiology Flashcards
What are the 3 levels of sexual dimorphism?
1) Genetic (M: XY, F: XX)
2) Gonadal (M: testes, F: ovaries)
3) Phenotypic
a) external genitalia
b) secondary sex characteristics
What gene encodes for the testis determining factor (TDF) and which chromosome is it located on?
SRY gene on Y chromosome
What is testis determining factor?
Nuclear transcription factor
- expressed in gonad immediately before divergence of ovarian/testicular development
- incites testis differentiation → formation of Sertoli and Leydig cells → produce MIS/Testosterone respectively
What is the key factor needed for the determination of male characteristics?
SRY/TDF
What are 5 genes that promote sexual differentiation in humans?
Male promoting:
1) SRY
2) SOX 9
Female promoting:
3) FOXL2
4) WNT4
5) FST
What essential hormone is produced by Leydig cells and what is its function?
Testosterone
- Wolffian duct development
What essential hormone is produced by Sertoli cells independent of FSH and what is its function?
Mullerian inhibiting substance/Anti-mullerian hormone (MIS)
- promotes Mullerian duct regression (to allow for Wolffian duct development)
What is Turner syndrome?
X0 chromosomal disorder
- F
- 1/2500
- Low IQ
- Infertile
- small stature
What is Klinefelter syndrome?
XXY chromosomal disorder
- M
- 1/700
- Low IQ
- Infertile
- Higher in stature
- Gynaecomastia/ small testes
What is hermaphroditism?
Having characteristics of both male and female
What is the difference between true hermaphroditism and pseudohermaphroditism?
True hermaphrodite:
- gonadal tissue and germ cells of both sexes present
- 50%: 1 testis/ovary + 1 ovotestis
- 30%: 1 testis + 1 ovary
- 20%: 2 ovotestes
Pseudohermaphrodite:
- inconsistency between internal and external genitalia
- 2 aetiologies:
i) Androgen insensitivity syndrom (AIS)/Testicular feminisation syndrome
ii) 5α-reductase deficiency
Describe the process of sexual differentiation in humans?
Male:
1) XY → SRY+
2) Testicular formation →
a) MIS → no mullerian duct → no uterus
b) Testosterone → (i) DHT (ii) Wolffian duct → Vas deferens, Epididymis, Seminal vesicles
3) DHT → Penis, Penile Urethra, Scrotum
Female:
1) XX/X0→ SRY-
2) Ovary formation →
a) No MIS → Mullerian duct → Uterus, Fallopian tube, Upper vagina
b) Estradiol → Clitoris, Labia minora/majora, Lower vagina
Describe the HPT axis in males.
Hypothalamus: GnRH
→ Anterior pituitary:
(i) LH → Leydig cells → Testosterone
- -ve feedback to AP and hypothalamus
(ii) FSH → Sertoli cells →
(i) Spermatogenesis
(ii) Androgen-binding protein w testosterone
(iii) inhibin
- -ve feedback to AP
Describe the function of GnRH.
Hypothalamus → GnRH → Gonadotrope cells in pituitary glands → FSH + LH
What are the hormones produced from the testes and which cells are they secreted from?
LH → Leydig cells → Testosterone
FSH → Sertoli cells →
i) Estradiol
ii) Inhibin
iii) Activin
iv) Follistatin
Inhibin and follistatin are secreted by ___________ and act to suppress _____ secretion.
Secreted by Sertoli cells under FSH stimulation
- act to suppress FSH secretion
- -ve feedback loop
What are 2 fates of plasma testosterone?
1) Estradiol (via aromatase in Sertoli cells)
2) DHT (via 5-α reductase)
3) Conjugated by liver
4) 17-Ketosteroids (via 17ß-dehydrogenase)
What are 6 functions of testosterone?
1) Control development of internal male genitalia
2) Support spermatogenesis
3) Support puberty
4) Support development of male secondary sex characteristics
5) Promote sex drive/libido (both M and F)
6) Promote protein synthesis and muscular growth
What is the enzyme responsible for DHT production?
5α-reductase
True or false. DHT is more potent than testosterone and thus its production is localised at specific target cells.
True
What are 3 effects of DHT?
1) Development of male external genitalia
2) Development and growth of prostate gland
3) Growth of male body/pubic hair (baldness)
What is the moa of DHT?
1) Testosterone diffuses across cell membrane
2) Testosterone converted to DHT by 5α-reductase
3) DHT binds to intracellular androgen receptor
4) DHT-AR complex undergoes dimerisation and phosphorylation
5) New complex passes through nuclear membrane to act at androgen-response element + recruits coactivator (ARA70)
6) Transcription of proteins → testosterone/DHT effects
How long does spermatogenesis take?
65-70 days
Describe the process of spermatogenesis.
1) Proliferation (3-4wks)
- Spermatogonium → 1° spermatocytes
- mitosis
2) Growth (3-4wks)
- 1° spermatocytes → 2° → spermatids
- meiosis
3) Differentiation (3-4wks)
- spermatids → spermatozoon
- Spermiogenesis
4) Maturation
- Spermatozoon → Mature spermatozoa
- in epididymis