Lecture 13Review of embryonic sexual development:*In this figure Anti Mullerian Hormone (AMH) is referred to as MIF*The prostate and the male external genitalia require DHT as well as testosterone to develop The embryo contains bi-potential gonads that begin to differentiate between 7-8 weeks. The cortex of these gonads will develop into ovaries, or the medulla will develop into testes if there isa functional SRY gene on a Y chromosome Wollfian ducts require testosterone to develop and degenerate in female embryosTestosterone also allows for the descent of the testes into the scrotum via the inguinal canal before birthPage 1 of 7BICD 150Sp’14Fortes75/13/141 of 7Testes have Leydig cells get stimulated by LH or placental hCG to secrete T. 5-a Reductase will convert some of this into DHT. T will stimulate the development of the wollfian ducts and DHT will cause male differentiation of the penis and scrotum. Sertoli cells will secrete AMH to cause degeneration of the mullerian ducts. Disorders of embryonic sexual development:- Mutated/nonfunctional aromatase: Low/no production of female hormones in the female embryo. Androgens including T will increase since it is not being converted to E2. There may be development of wollfian ducts since T is high. - Mutated/nonfunctional 5-a Reductase: No conversion of T into DHT. External genitalia will develop as female. There will also be little to no growth of the prostate. Wollfian ducts will still develop into male accessory structures since there is still T being secreted by the testes. Mullerian ducts degenerate due to the secretion of AMH. o There are drugs that can be prescribed that inhibit 5-a Reductase. These are usefulto treat hypertrophy or enlargement of the prostate in aging males, since DHT is what stimulates its growth. - Non-functional androgen receptors: “Testicular Feminization”. Testes will still be present due to the SRY gene. Sertoli cells secrete AMH to degenerate the mullerian ducts. Leydigcells secrete T, which can be converted to DHT, but there will not be any effects due to the lack of receptors. Wollfian ducts also degenerate due to the lack of effects of T. Female external genitalia due to lack of DHTs effects. Hormonal Effects during Puberty:GnRH starts pulsing to initiate puberty and the secretion of FSH and LH. These hormones stimulate the gonads to greatly increase secretion of E2 or T. The age of onset of puberty has been decreasing. This has been attributed to better nutrition. However, it is now believed that childhood obesity is contributing to earlier puberty. - In 1994 a hormone secreted by adipocytes was discovered called Leptin. It was discovered that mutant rats/mice that could not produce the hormone were extremely obese. Leptin is an important appetite inhibitor. The mice also did not undergo puberty. Itis believed that Leptin is an important signal to begin puberty. - Obese children have larger and more numerous adipocytes and more leptin is secreted. This could cause earlier puberty. Female:- Earlier growth spurt than boys- Development of breasts- Development of female pattern pubic hair; inverted triangle - Axillary hair - Redistribution of fat under the effect of E2; female “hourglass” figure Page 2 of 7- Menstruation - AcneMale: - Deepening of voice- Development of facial hair - Growth of penis and testes- Growth spurt- Broadening of shoulders- Increase in muscle mass- Acne Hormonal changes after puberty:Males remain fertile throughout their lives after puberty. However, the ability of the testes to secrete T and DHT decreases with age. This generally causes an increase in FSH and LH. T and E2 inhibit bone resoprtion. Low levels of T/E2 will cause an increase in bone resorption that can lead to osteoporosis, this is more common in again females however. Females go through menopause generally in their early 50s. All ovarian follicles have been ovulated or have died. This causes an enormous drop in estrogens that normally come from the ovaries. Some E2 is still made by peripheral conversion of androgens from the adrenal cortex viaaromatase, but it is greatly reduced.- No longer menstruate- Increased osteoporosis- “Hot flushes/flashes”End of Reproduction! Lecture let out ~25 minutes early today. Enjoy the great weather!Page 3 of 7Lecture 14: Pancreatic hormonesThe pancreas has both exocrine and endocrine function- It secretes bicarbonate rich pancreatic juice to neutralize stomach acid as well as inactive digestive enzymes known as Zymogens into ducts that lead into the small intestine in an exocrine fashion. As an endocrine organ, the pancreas secretes several hormones from a variety of cell types called“Islets of Langerhans”:- Alpha cells: 25% of Islet volume; Secrete Glucagon- Beta cells: 55% of Islet volume; Secrete Insulin and C Peptide- Delta cells: 10% of Islet volume; Secrete Somatostatin (inhibits mainly glucagon secretion as well as insulin to an extent)- Epsilon cells: 3% of Islet volume; Secrete Ghrelin (hormone mainly secreted by the stomach that is known to increase appetite)Insulin and Glucagon regulate metabolism and blood glucose levels in an antagonistic “yin/yang” fashionInsulin: Hormone of the “fed state” that “makes you fat”- Eating and absorbing nutrients will stimulate its secretion - Promotes Anabolism- Increase Lipogenesis- Increase Protein synthesis- Glycogen synthesis- Increase carbohydrate metabolism - Is a growth factor; has mitogenic effectsPage 4 of 7BICD 150Sp’14Fortes75/15/144 of 7Glucagon: Hormone of the “fasted state”- Increases availability of substrates to be used for energy when you haven’t eaten/food is low- Catabolism - Increase Lipolysis - Increase Glycogenolysis - Increase Gluconeogenesis - Increase protein breakdown in extreme casesThe secretion of insulin and glucagon are both extremely dependent on blood glucose levels- High blood glucose stimulates insulin and inhibits glucagon - Low blood glucose stimulates glucagon and inhibits insulinInsulin:- A protein secreted by the beta cells- Proteins that are destined to be exported from cells are synthesized as larger precursors inthe rough ER where they are folded - From there, vesicles containing the precursor proteins are sent to and further processed inthe Golgi - Vesicles containing the final form of the protein are then exocytosed upon receiving the appropriate signal - Synthesized as Pro-Insulin and cleaved into Insulin and C-Peptide by proteases - C-Peptide has