IPHY 4440 1st Edition Lecture 20 Outline of Last Lecture I. Mineralocorticoids II. RAS (Renin-Angiotensin System)III. Actions of A2I. RAS regulationII. Atrial Natriuretic PeptideIII. Clinical aspects of adrenal disorders Outline of Current Lecture IV. Clinical aspects of adrenal disorders continued V. Development of the Reproductive System VI. Sex differentiation VII. Disorders of human differentiationCurrent LectureI. Clinical aspects of adrenal 1) GC HyposecretionAddison’s Disease: primary low GCs, elevated ACTH, Hyperpigmentation: because of elevated ACTH similar to Cushing’s syndrome -Causes to secreted too much aldosterone?  Primary hyperaldosterone: tumor in zona glomerulosa: pump out aldosterone uncontrollably  Tumor in JG cells making renin uncontrollably in the kidney  Serious problems with hypertension  Abnormal balance: cannot fire action potential properly 2) Aldosterone disorders hyperaldosteronism: decrease in potassium/increase in sodium= muscle weakness 3) Adrenal androgen disorders: CAH= congenital adrenal hyperplasia (21-hydroxylase deficiency) P450c21 (P®®GC) 90-95% of cases- 21-hydroxylase deficiency: masculination of female prior to birth, short stature, and salt balance problems - Masculinization of female prior to birth?? 2 reasons: These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- 1) Decrease GCs (these ppl cant make these bc P450c21 is not functional),increase in ACTH, stimulate z. r. to increase androgens - 2) Since steriodogeneis is a sequential process, when disrupt a little part then becomes a domino effect, disrupt entire pathway  so increase in progesterone and goes to a different pathway aka delta 4 pathway converts to AND then  increase in T - And that’s why they get a lot of androgen (Testosterone) - Why would they have short stature? Because they have high androgen levels- Salt balance problems? No aldosterone II. Development of the Reproductive System Sex is determined by genes (only in mammals) A. Male is heterogametic (XY) Maleness is defined by testes, produces  sperm (small gamete)B. Female is homogametic (XX) Femaleness is defined by one having ovaries, produces  eggs (large gamete)C. SRY gene: on Y chromosome, genetic basis for sex determination (only in male determination)- (XY) SRY  testis determining factor  testis- (XX) No SRY  by default  ovary forms III. Sex differentiation Differentiation of: 1) Reproductive tract 2) External genitalia  Sex differentiation is actually driven by hormones not by genes A. Differentiation of sex reproductive tract1) Wolffian duct: allow to grow and mature into male reproductive tract include: vas deferens, seminal vesicle, epididymis 2) Mullerian duct: allow to grow and mature into female reproductive tract which includes: oviduct, uterus, vagina3) If fetus is male: Testis  T & Mullerian Inhibiting Substance (MIS)  wolffian duct maintained and Mullerian duct degenerates4) If fetus is a female: No testis  No testosterone & No MIS  wolffian duct degenerates and Mullerian duct maintained IV. Disorders of human differentiationA. Pseudohermaphroditism: mutations in right gonad and wrong ducts and genitalia1) Most famous ex of this: Testicular feminization syndrome(androgen-insensitivity syndrome) No functional androgen receptor- so chromosome: XY, Gonad: testis, Duct: none, Genitalia: female, Phenotype: female2) 5a-reductase deficiency (Guevedoces)-Dominican Republic Lacks 5a-reductase- Genitalia: female first (no DHT) then male at puberty (increase T) - Phenotype: female first (no DHT) then male at puberty (increase T)Facial hair, grow a penis 3) Congenital adrenal hyperplasia - Most common pseudohermaphroditism (50%)- androgen immediately before ® after