Flashcards in Lecture 27: Sex Steroid Synthesis Deck (78)
What is DHT? How is it synthesized? Where?
More potent form of testosterone responsible for balding
5-α-reductase: testosterone + NADPH => dihydrotestosterone (C5/6 double bond reduced) + NADP
This happens in target tissues (not much in testes)
What does the enzyme 17-β-hydroxysteroid dehydrogenase do? Mechanism, substrates, products?
- Mechanism: C17 ketone to hydroxyl
- Substrates: DHEA and androstenedione
- Products: androstenediol and testosterone
What does the enzyme aromatase do? Mechanism, substrates, products?
- Mechanism: 3 hydroxylations making the first steroid ring aromatic + C3 ketone into hydroxyl using 3 NADPH and 3 O2 + C19 is removed = P450 complex
- Substrates: androstenedione and testosterone
- Products: estrone and estradiol
What is the difference between the synthesis of sex hormones in the adrenal cortex vs testes/ovaries?
- Adrenal cortex: ACTH stimulation
- Testes/Ovaries: LH stimulation
Can the testes/ovaries make glucocorticoids and mineralcorticoids?
Where are 3-β-hydroxysteroid dehydrogenase/Δ5-4 isomerase more active: adrenal cortex or testes/ovaries?
How can male baldness be treated?
Where are estrogenS synthesized?
1. Adrenal cortex
3. Adipose tissue
4. Placenta/Fetal Liver
What is gynecomastia? What are its 5 causes? 2 Treatments?
Male breast development due to:
1. Extra fat causing extra estradiol synthesis
2. Exogenous testosterone or anabolic steroids cause excess substrate for aromatase
3. Puberty causing excess androgens being converted to estrogens (seen in 50% of men)
4. Old age (70% of men)
5. Androgen insensitivity syndromes
Treatment: anti-androgen therapy or surgery
Where are the enzymes 17-β-hydroxysteroid, aromatase, and 5-α-reductase located inside the cell?
Describe the regulation of testosterone synthesis.
1. Hypo releases GnRH
2. Ant. Pit. release LH/FSH
3. LH stimulates Leydig cells to produce testosterone/FSH and testosterone stimulates Sertoli cells to produce ABP and inhibin
4. Testosterone exerts negative feedback on hypo and ant pit/Inhibin exerts negtive feedback on ant pit
What is ABP?
Androgen binding protein in the seminiferous tubules
Describe the binding of ABP and testosterone?
What is responsible for fertility in men?
The high concentration of testosterone in the testes (bound to ABP in seminiferous tubules) enables spermatogenesis
Why do anabolic steroids lead to infertility?
Anabolic steroids => high concentrations of androgens in blood => negative feedback on hypo and ant pit => less testosterone synthesis in the testes binding to ABP => infertility
What are the 2 blood binding proteins of testosterone? Describe their binding.
1. TeBG (strong)
2. Albumin (weak)
Other than to testosterone, what can TeBG bind in the blood?
1. Estradiol (weak)
What % of testosterone is free in blood?
What's are the 2 differences between ABP and TeBG?
1. Same primary sequence (come from same gene) but different glycosylations
2. ABP binds testosterone in seminiferous tubules of testes vs TeBG binds testosterone in blood
To what kind of receptors do testosterone and DHT bind?
SAME nuclear receptors (but different physiological effects)
What are the 3 effects of testosterone binding to its nuclear receptor?
1. Gonadotropin regulation
3. Wolffian stimulation = vas deferens, epididymis, seminal vesicles
What are the 3 effects of DHT binding to its nuclear receptor?
1. External virilization
2. Sexual maturity at puberty
3. Penis, penile urethra, and scrotum development IN UTERO
How can testosterone and DHT have different effects when they bind to the same nuclear receptors? 2 mechanisms
1. Upon binding they induce different conformational changes allowing the hormone-receptor complex to bind different transcriptional coactivators
2. DHT binds more tightly than testosterone
What is hypogonadism? 2 causes? 2 symptoms? Possible origin?
Not enough androgens/testosterone produced
- Causes: fault in testes (primary hypogonadism usually due to genetic deficiency for an enzyme needed for synthesis) or fault in ant pit (secondary hypogonadism)
- Symptoms: failure or regression of secondary sex characteristics
When can a small penis be treated? How?
Before puberty if there has been a failure of androgen production by using an androgen cream on the penis (no more receptor on penis after that)
What is 5-α-reductase deficiency? 3 Symptoms?
Male inability to produce DHT: FEMALE looking BABY starts looking like A MAN AT PUBERTY
1. Male internal genitalia (inguinal testes: have not fallen but still produce testosterone) but external female genitalia (no penis, penile urethra, nor scrotum)
2. Ambiguous genitalia: cliteromegaly or micropenis
3. Certain degree of masculinization during puberty: "penis" growth, testes fall down, but urethra is at the base of the penis
What is Complete Androgen Insensitivity Syndrome (CAIS)? 2 Symptoms?
No androgen receptors in males
1. Total failure of male phenotype development, except they have testes producing androgens
2. Female phenotypical features: breast, little/no sex hair due to conversions of androgens to estrogens
What is the main estrogen for premenopausal women of childbearing age?
Where is estradiol produced?