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Testes have two main functions:
- Synthesis of androgens
- Gametogenesis
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Androgens (testosterone) are C__ compounds,
Estrogens (estradiol) are C__ compounds
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_____ cells and _____ cells are the major components of the seminiferous tubules. ____ cells, aka ______, lie between the tubules.
- Sertoli
- germinal
- Leydig
- interstitial cells
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_____ cells secrete 4-10 mg testosterone daily (~95% of the circulating testosterone)
Leydig
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Leydig and Sertoli cells are engaged in a cross-talk:
- Leydig synthesize testosterone which diffuses into seminiferous tubules to maintain spermatogenesis
- Sertoli cells synthesize
- 1. P-450 aromatase that converts testosterone to estradiol.
- 2. Androgen binding protein (ABP) that binds to testosterone.
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Circulation and mechanism of action of testosterone
- ~2% circulates freely
- 45-65% bound to sex hormone-binding globulin (SHBG)
- The rest bound to serum albumin
can be converted to dihydro-testosterone (DHT) by the 5α-reductase enzyme in target cells, similar to glucocorticoids and mineralocorticoids: both bind to cytoplasmic androgen receptor, release HSP, dimerization, activate transcription of genes by binding to an estrogen-like hormone response element (ERE)
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Which androgen has the higher potency, DHT or testosterone?
DHT
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Testosterone induces transcription of genes that encode for proteins involved in:
- Growth/development
- Sexual differentiation
- Gametogenesis
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Functions of androgens
- On growth and development on somatic tissues: anabolic
- On development and growth of the male reproductive tract and of secondary sexual characteristics: androgenic
- So far, no synthetic steroids have discriminating effects
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Sexual Differentiation of the testes
- formation of sex cords that incorporate the primitive germ cells; ~7th week
- secretion of AMH and involution of Müllerian ducts
- Leydig cells appear and secrete antrogens, essential to the masculinization of the fetus
- the Wolffian ducts develop into the epididymis, the vas deferens and the seminal vesicles
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The initial steps of sex differentiation of testes are driven by __________, the gene of which is located on ___________.
- Testis determining factor (TDF)
- Y chromosome
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sex cords is the future ______
Sertoli cells
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By the 8th fetal week, Leydig cells appear in the differentiating testis and begin to secrete androgens, the actions of which are essential to the ________ of the fetus.
masculinization
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With the regression of the ________ and under the influence of _________, the Wolffian ducts develop into the _______, the _______ and the _______.
- Müllerian ducts
- testosterone
- epididymis
- vas deferens
- seminal vesicles
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DHT is responsible for ______.
the urogenital sinus and external genitalia development
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Gametogenesis:
•Spermatogenesis is under the control of ______ secreted by ________ and greatly affected by ______
•________ provide the support
•3 processes occur concurrently in the tubules:
- testosterone
- Leydig cells
- temperature
- Sertoli cells
- • Mitosis (increase in number of cells)
- • Meiosis (reduction in number of chromosomes)
- • Spermiogenesis (production of mature sperm)
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Secretion of steroid by testes is under the control of the ______. ______ produces the ________, which stimulates _______.
- hypothalamopituitary axis
- Hypothalamus
- gonadotropin-releasing hormone (GnRH)
- in the anterior pituitary gland the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH)
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LH and FSH are the primary ______ that stimulate testicular function:
LH acts on _____ cells, just like ____ on ____, to synthesize _____ and increase:
- gonadotropins
- Leydig
- ACTH
- adrenal cortical cells
- Enzymes involved in testosterone biosynthesis and sterol-carrier protein (SCP-2) involved in cholesterol transport across mitochondrial membrane
- • intracellular concentrations of free cholesterol,
- • its transport to the mitochondria
- • Conversion of cholesterol to pregnenolone by P450scc
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FSH: acts on _____ cells to stimulate _____ synthesis, mobilization of ______, production of ______, and the output of proteins such as ________.
- Sertoli
- protein
- energy resources
- testicular fluid
- inhibin, ABP, P450 aromatase, AMH and 5α-reductase
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Functions of following Sertoli cells products
Aromatase:
Inhibin:
- converts testosterone into estradiol
- exerts a negative feed-back on FSH secretion
-
______ stimulates _______ LH and FSH
_______ of the proteins occurs in ______
LH and FSH act on ____ cells via _____
- GnRH
- transcription of the genes coding for
- Glycosylation
- the pituitary gland
- gonadal
- GsPCR and GqPCR, and GsPCR
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•One testis can produce ____ sperm/day
•Sperm maturation occurs in ______
•Sperm can be stored up to ____ in _________.
- 200 million
- the epididymis
- 5 weeks
- the tail of the epididymis and vas deferens
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•Sensory stimulation induced _____
•________ and ______ engorged with blood which results in erection.
• At ejaculation the semen (_______) is expelled from the ______
- vasodilatation of arterioles
- Corpus spongiosum
- cavernosum
- sperm +seminal fluid
- posterior urethra
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(Erection-inducing) vasodilatation is under the control of the ______ pathway:
- NO-cGMP
- NOS (nitric oxide synthase) -> NO -> soluble GC -> cGMP -> vasodilation
- cGMP -phosphodiesterase-> GMP
- Viagra (sildenafil) inhibits phosphodiesterase
-
5α‐reductase deficiency (___________)
- hermaphrodism
- ambiguous genitalia at birth due to impaired external genital development
-
AR deficiency ‐ Due to mutation(s) in the androgen receptor
Various degrees of androgen insensitivity syndrome (AIS) ‐ In 46XY with complete AIS, ________ (phenotypically _____).
- no proper development of external and internal genitalia
- female
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