Lecture 6 Endocrine Regulation of Male Reproduction 2 Flashcards
What primitive structures form male external genitalia?
Genital ridge become external genitalia.
Including genital tubercle which grows to shape itself around urethra thus becomes penis. And labioscrotal swelling fuse and form scrotal sac
How are the female external genitalia formed?
Genital tubercle is not stimulated so does not form penis, instead becomes clitoris.
Labioscrotal swelling remains unfused so from labia majora and minora
How is Wnt signalling different in external and internal genitalia?
Wnt signalling drives female internal genitalia. But drives male external genitalia.
How is male external genitalia formed?
Androgen and androgen receptor blocks Wnt inhibitors so increases Wnt/ß-catenin activity, thus causes formation of penis and scrotum
How is female external genitalia formed?
Due to the lack of androgen and its receptor, there is Wnt inhibitory effect, hence no Wnt/ß-catenin activity, so no formation of penis/scrotum, instead forms vagina and clitoris
If in a female, there is no Wnt activity, but genetically modify expression of ß-catenin, what would happen?
No testes so no testosterone/DHT, thus internal genitalia would be ovary. However due to ß-catenin activity there will be formation of penis and scrotal sac
What is observed in a male individual with Androgen Insensitivity Syndrome?
Male so has XY, so has SRY protein, stimulating testosterone and AMH synthesis, thus will have testes in internal genitalia. But because androgen receptor is mutated it is not sensitive to androgen, so cannot inhibit Wnt/ß-catenin activity thus forms female external genitalia. Furthermore elevated testosterone will have elevated oestrogen due to aromatase action, however no testosterone negative feedback because androgen receptor is not sensitive
What is the role of DHT?
Drives differentiation of male external genitalia as it inhibits Wnt inhibitor. Also maintains epididymal cells and epididymal secretions. And essential in sperm maturation.
What happens in 5 alpha-reductase II deficiency?
Reduced conversion of testosterone to DHT. Because testosterone is present testes will form. However due to lack of DHT, external genitalia is female at birth. Shockingly at puberty, rapid onset of male sex characteristic: activation of HPG, descending of testes, development of penis from clitoris and labia
Are oestrogen and oestrogen receptors present in testes, epididymis and ejaculated sperm?
Yes
What is the function of oestrogen in the male reproductive tract?
Maintenance of spermatogenesis in seminiferous tubules. Fluid reabsorption and regulation of epididymal fluid necessary for sperm maturation, in efferent ducts (connection between testes and epididymis) and proximal epididymis.
Illustrate oestrogen regulated water reabsorption.
Proteins and exchangers regulated by oestrogen receptor alpha and beta.
H2O is reabsorbed from luminal into basal through aquaporins, gradient set up by movement of Na+ in the same direction (via NHE3 sodium proton exchanger on luminal side, and ATPase on basal side). Furthermore DRA HCO3- Cl- exchanger protein and CFTR balances ions.
Illustrate observations in a ERalpha-KO male mouse
Lack of oestrogen receptor alpha downregulates the NHE3 sodium-proton exchanger so less Na+ moves from luminal to basal. Hence smaller gradient so less water reabsorbed. Increased pressure in lumen, so distended seminiferous tubules and disrupted spermatogenesis, leading to infertility
Illustrate observations in a ERbeta-KO male mouse
Lack of oestrogen receptor beta upregulates activity of DRA and CFTR causing more ionic movement into lumen and hence more water moving into lumen through aquaporins. Leads to dilute luminal fluid but not serious enough to cause infertility.
How is prostate growth affected by hormones?
DHT, oestrogen, and prolactin promotes androgen receptor expression which has a positive effect on growth factors of prostate.
