Male Reproductive Flashcards
Sex differentiation/ determination
- Genetic sex (XY or XX) determines ovary (from unknown gene) or testis (from SRY gene) differentiation
- Gonads determine phenotypic sex: testes secrete testosterone and AMH –> male phenotype; DHT to fully develop external genitalia. Without fetal male testosterone/AMH (or functional receptors) –> female phenotype
Development of male phenotype
- SRY gene expression from the Y chromosome determines testes differentiation
- Testes’ Leydig cells produce testosterone –> Wolffian duct development (male reproductive tract); programming of hypo and sexually differentiated brain areas
- testosterone converted to dihydrotestosterone (DHT) –> External male genitalia develops
- antimullerian hormone (AMH) from testis –> mullerian duct regresses
Development of female phenotype
- no testosterone–> no programming of hypo and sexually differentiated brain areas
- no DHT –> female external genitalia (clitoris, labia, lower vagina)
- no AMH –> mullerian duct develops into fallopian tubes, uterus, upper vagina.
- **ovaries secrete minimal steroid hormones during fetal life
Development if a female ovariectomized just as the fetal ovaries start differentiating
Still have female parts (minus the ovaries).
Development if a male is castrated just as the fetal testes start differentiating
Testes secrete testosterone and anti-mullerian hormone (AMH). Castrated = No testicles = No Male hormones = Persistent mullerian duct with no AMH= a female phenotype develops, including the lower vagina.
Development if a female ovariectomized just as the fetal ovaries start differentiating, that then receives fetal male levels of testosterone throughout gestation
Female and Male reproductive tracts + external male genitalia including Penis.
Development if a male is castrated just as the fetal testes start differentiating, that then receives fetal male levels of testosterone throughout gestation
Would have normal testosterone levels because supplemented but no AMH so you would have both Wolffian and Mullerian duct derivatives with male external genitalia
Development if a male with 5-alpha reductase deficiency
- 5 alpha converts testosterone to DHT for external male genitalia
- Still have testosterone, so programming of the hypothalamus and sexually differentiated brain areas. However, NO DHT can be made because 5aR deficiency, so patient will have female external genitalia.
Development if a normal, ovary-intact female receiving fetal male levels testosterone throughout gestation
Female and Male reproductive tracts + Penis
Development if an XY individual with defective androgen receptors
- Sertoli cells secrete AMH → No female reproductive tract
- No testosterone receptor activity–> No male reproductive tract development from the Wolffian duct (e, vd, st), No prostate, B. glands, penis, or scrotum–> Female somatic phenotype, including a blind vaginal pouch (because upper ⅔ is from Mullerian duct).
Development if an XY individual with bio-INactive AMH
- Male phenotype and Male external genitalia.
- Female reproductive tract (from the Mullerian Duct) with fallopian tubes
- Male reproductive tract (from the Wolffian Duct) but undescended testes which can cause unilateral inguinal hernia because oviducts and uterus get stuck.
- Risk for unilateral inguinal hernia (because testes strung up with a ligament to the ends of the fallopian tubes)
Sertoli cells
- have FSH receptors → inhibit B synthesis and release
- regulates sperm maturation by making estradiol (which is dependant on Leydig cell testosterone production)
- produce AMH which is required to shut down the Mullerian pathway to female internal tract
- produce DHT
Leydig cells
have LH receptors–> testosterone synthesis and release
Spermatozoa
result from spermatogenesis in 70 days, produce 100-200 million spermatazoa per day
Sex-hormone binding globulin (SHBG)
In circulation, the predominant bioactive androgen, testosterone travels bound to SHBG. because testosterone is only active when unbound to SHBG, the binding globulin buffers changes in testosterone concentration.
SRY gene
gene from the Y chromosome that determines testes differentiation.
Luteinizing hormone (LH)
from anterior pituitary → leydig cells → testosterone → sertoli cells → sperm maturation
Follicle stimulating hormone (FSH)
stimulates aromatase in sertoli cell → conversion of testosterone from leydig cells into estradiol (E2) → supports testosterone regulation of LH and GnRH and inhibin B regulation of FSH
Testosterone
develop male tract, high levels negative feedback on LH release, crosses BBB, decreases GnRH. Normal levels at 300-800 ng/dL
Inhibin B
produced by Sertoli cells, negative feedback on FSH
List the effects of testicular androgens on male anatomy, physiology and reproductive function
- Enlargement of larynx and vocal cords
- Development of male musculature and fat deposition (anabolic effect)
- Growth of pubic, axillary and facial hair
- Growth and development of penis and scrotum (no additional effect on penile size post-puberty)
- Stimulation and maintenance of spermatogenesis starting at puberty
- Maintenance of accessory sex glands
- Support of cognitive function
- Increase in libido at puberty
- Support of bone mineralization, including aromatization to E2 (estradiol)
How does the pattern of testosterone secretion by the testes vary over the course of a male’s lifetime from fetal differentiation of the testis into old age?
- 4-5 months after fertilization: peak up to 1100 ng/ml
- neural inhibition of GnRH during childhood
- age 10-20: increases up to 1100 ng/ml
- aged 40-70: Total testosterone decreases 0.8% per year, free testosterone declines 2% per year
Estradiol in males
- produced by Sertoli cells
- supports testosterone regulation of LH and GnRh, and inhibin B regulation of FSH (produced in testes or aromatized in hypo/pituitary from Testosterone)
Male negative feedback regulation of testosterone
- Hypothalamus GnRH neurons release GnRH into portal veins
- binds GnRH receptor in anterior pituitary, stimulates gonadotropes to release LH into blood
- LH binds receptor in Testes
- stimulates Leydig cells to release testosterone
- testosterone stimulates sertoli cells –> sperm
- testosterone does negative feedback: binds androgen receptors in anterior pituitary and hypothalamus
- *also targets tissues –> targets include skeletal muscle, brain, hair follicles, genitals, etc.
