Sex Determination and Development

Sex Determination and Development
A person’s sex has 5 meanings- see first sheet.
Y chromosome has SRY gene- causes primordial gonads to become testes- otherwise they are ovaries.
TDF- testis determining factor makes primordial gonad become a testis. What is this factor? Not quite known.
figures 9 and 10 in Johnson, page 729 for illustration of how gonads become ovaries and testes. Female- Mullerian ducts predominate. Male- Wolffian.
Remove gonads- without testes- get female pattern. Remove one testis, get male gender on the intact side, female ducts on the other without ovary (testis removed).
MIS-Mullerian inhibiting substance- active to cause development of Wolffian ducts.
Muscle growth in men is induced by androgens. Steroids influence gonadotrpoin secretion.
General pattern of Hormonal control:
Hypothalamus secretes GnRH to Anterior pituitary. Gonadotrophs secrete LH and FSH. LH and FSH are the same male and female. Cell type A in males and females synthesizes and secretes androgens (M-testosterone, females testosterone and other androgens). The androgens diffuse to affect type B along with FSH to promote development of germ cells. Type B tends to secrete inhibin which feeds back negatively to the pituitary gland to reduce secretion of FSH. Gonads also release substances that affect skin, brain , muscles in stimulatory or inhibitory ways.
Effect of androgen- affects pituitary(Reduces LH, and reduces FSH at high doses) and hypothalmus (affects GnRH) in a negative way. Feedback inhibition. gonadotrophs under inhibition respond less to what GnRH they do get than they usually would.
Male Reproductive System
for testes to produce sperm, they function lower than abdominal temperature. Temperature is maintained about 1- ½ degrees C lower by testicular movement, hair (to insulate to stay warm) and sweat glands, circulatory system. Humans cannot pull in testes completely (rats can).
Ram (diagram in notes)- big temperature differential. Countercurrent heat exchanger. Warmer blood of arteries gives up heat to cooler venous blood. This occurs in the pampiniform plexus. Arteries and veins are highly coiled and intertwined.
Semen is the product of testes plus accessory glands. Most volume from seminal vesicles (60%),then prostate, then sperm.
Testes- Leydig cells produce testosterone. See diagram from text, figure 1 page 721. Sperm are produced at edges of tubules. Interstitum has Leydig cells. Tubular lumen- Sertoli or nurse cells facilitate development of sperm from primary spermatogonia, to spermatocyte, to spermatid, to spermatozoa, to mature sperm.
High concentration of testosterone are due to LH and GnRH. (2 indirect hormones)
Why is there a high concentration of testosterone? Produced by Leydig cells and diffuses across to Sertoli cells. These respond to FSH and testosterone to enhance production of sperm. If there are no Leydig cells, a really high dose of testosterone is necessary to produce sperm.
Tight junctions keep materials in circulation from reaching sperm. Protects sperm from materials in blood.
Sertoli- nourish development of sperm.
blood-testis barrier is a barrier to chemicals. It protects sperm from harm to som extent.
ABP (androgen binding protein) binds testosterone and carries along with sperm. Sertoli cells phagocytose defective sperm. Size of cytoplasm is greatly reduced during sperm development. Sertoli cells do this. Not all defective sperm are detected.
Testosterone shows some diurnal variation, but it is considered pretty steady compared to monthly cycling of females.
Some testosterone must be activated to be effective. DHT activation occurs in target cells. DHT binds receptor, goes to nucleus, affects gene transcription.
Testosterone can be converted to estrogen by aromatase. This happens in brain, pituitary, liver, breast, adipose tissue. Obese boys get apparent mammary gland development from higher estrogens from adipose tissues promoting fat deposition in mammary areas.
Degradation:
1. 5B reductase.
2. 17-OH->17keto->17-ketosteroids
3. conjugation with sulfate or glucoronate
4. urinary excretion- measure 17-KS in urine.
17-KS in person with liver disease decreases. Adipose tissue may convert excess testosterone to estrogens.
Do not have to know or replicate diagram of synthesis.
All steroids start with cholesterol. Androstenediol and dione are weak androgens. Most potent is testosterone. Enzyme making DHT is 5-alpha reductase. 5-beta reductase inactivates testosterone. Aromatase makes estradiol. All can be converted to water-soluble metabolites.
Tables indicate steroids in adult men and cycling women. Do not know numbers- look at patterns of similarity and units.
Most testosterone is bound, but only free can get out to target tissues.
Androstenedione and testosterone in both genders affect sex drive.
Men and women have PRL. May act on testes.
Other table- adult men. Most testosterone from testes. Most DHEA from adrenal glands- chief adrenal androgen.
Transport testosterone: see paper.
Know the lists for testosterone, estrogen, progesterone.
Testerone does not cause baldness. Genes do. Test allows it to happen. i and j are controversial.
General Pattern diagram:
A. Leydig cell. B-Sertoli cell.
Female Reproductive system:
See outline on paper.
Average menstrual cycle about 28 days long. day 0 is 1st day menstruation. Menstruation lasts 4-5days. Cells are sloughed off. Repairs and grows first half of cycle- ends at ovulation. Variations in length of cycle are due to variation in first part of cycle. Growth in new follicles is stimulated by FSH at end of previous cycle. In the middle, high estrogen causes midcycle surge of LH and FSH- LH triggers ovulation. then 2nd half.
Estrogen is high twice in the cycle, progesterone high only in second half.
As cells grow, they die and slough off. Midcycle with high estrogen- cornification- cells look like corn flakes. Sign that vagina has seen high levels of estrogen.
Estrogens are antiatherogenic. Increase HDL/LDL ratio. Estrogen increases HDL and decreases LDL. Estrogens
10f: increases suppleness, collagen content, water content of skin. Estrogens are added to some skin care products because of this.
Progesterone and progestigins :
5. BBT is basal body temperature. Ways to raise body temperature- muscle activity, coffee.
BBT measured same time every day, first thing in morning. BBTin mid -cycle dips, then rises. Higher temperature second half of cycle during increase of progesterone.
Ovary-
Both ovaries, each cycle- some primordial follicles start growing. dominant one on one ovary goes to surface. Mature follicle bulges, ruptures, egg released. The remaining granulosa and thecal cells turn into corpeus luteum (yellow from lipid)- makes progesterone and estrogen. Antrum is fluid- high in estrogen. Thecal cells produce testosterone, which gets turned into estrogen.
We still do not know what substance inhibits follicular growth. Follicle becomes atretic.
Inhibin decreases FSH secretion near the end of the follicular phase.
Another factor- GnSAF or GnSIF- gonadotropin cycle surge attenuating/inhibiting factor. Inhibits until dominant follicle is ready to release ovum.
To increase number of follicles, give FSH. Get multiple children. To get ovulation- treat with LH-like hormone.
Corpus luteum starts to develop as progesterone starts to rise.
hCG is human chorionic gonadotropin. It comes from placenta. Blastocyst implants and develops placenta- chorion produces chorionic gonadotropin to keep corpus luteum from regressing- continues to secrete estrogen and progesterone for successful pregnancy.
hCG goes up before end of 2 weeks to keep corpus luteum from degenerating. See text.
Ovary is key in regulation. Ovary regulates by estrogen it secretes. Need one functional ovary, portal connection, listed things in C.
Hypogonadal- low estrogen and progesterone. Hypogonadotropic- no pulsatile GnRH. Treat with pulses GnRH, stimulates ovaries. GnRH must be administered in pulses.
Reproductive Aging
Know difference hCG(LHlike) and hMG(FSH like)
Thelarche (pronounced "thelarkee") is beginning of breast development. Adrenarche or pubarche= hair growth. First period is after these. First ovulation may be around 13-14.
Boys- increase in FSH, testicular size, LH up, testosterone up, other events start at same time.
Pregnancy
1. egg drawn into open end of oviduct. See paper for the rest.
hCG keeps corpus luteum working first 2 months. Estrogen and progesterone increase throughout pregnancy- from placenta after 1st 2 months. hPL- human placental lactogen or hCS- comes from chorion- acts like prl and GH. Gets mammary gland ready.
Page with physical changes- lots of systems altered in pregnancy. You do not have to memorize these.
Please note that a LOT of the notetaking for this involved drawing arrows in little blanks on the paper he handed out in class. See paper for someone who was there.