Endocrinology of Reproduction Lecture 8 part 1 // Cramberry: Create & study flash cards online

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what is released in the hypothalamus and how is it released? The hypothalamus releases Gonadotropin Releasing Hormone (GnRH). It is released in a pulsatile fashion and acts on the gonadotropes of the anterior pituitary to induce FSH and LH secretion by phospholipase C signaling.

What does the Anterior Pituitary Gonadotropes release and what cells do those secreted cells affect? The Gonadotropes release Luteinizing Hlormone (LH) and Follicle Stimulating Hormone (FSH). The LH acts on the Leydig cells of the testis or the Theca cells of the ovary. The FSH acts on Sertoli cells of the testis or Granulosa cells of the ovary.

What are the steroid "sex" hormones that gonads can release? Testosterone, Estrogens (esterone (E1), estradiol (E2), and estriol (E3)), and Progesterone (P).

Where is testosterone released from and what does it do? Testosterone is made by the Leydig cells of the testis. It inhibits LH release in the AP and decreases GnRH release in the hypothalamus. It is converted to the more potent dihydrotestosterone (DHT) by the enzymes 5alpha-reductase 1 and 2.

Where are Estrogens made and what does it do? Estrogens (esterone (E1), estradiol (E2), and estriol (E3): Androgen (A) precursors (androstenedione and T) are made by the theca cells of the ovary. FSH induced enzyme aromatase convert A to the estrogen forms. Aromatase inhibitors are effective against E-Dependent cancers. Estriol is a fetal adrenal/liver-placental product. Early in the menstrual cycle, moderate steady levels of estrogen inhibit LH release while before ovulation, rising levels of estrogen increase LH release by increasing the number of GnRH receptors on the gonadotropes.

Where is Progesterone released from and what does it do? Progesterone (P) is produced by the corpus luteum after ovulation (and by the placenta during pregnancy). It is synergistic with E2 and P inhibits GnRH release.

In plasma, what is the condition of steroid (sex) hormones? 98% of all sex steroids are bound. 2/3 of all T are carried via Gonadal Steroid Binding Globulin (GBG) and 1/3 of all T by albumin. The opposite ratio is true for E2 in males. Female ratios vary within the mentrual cycle since E increases GBG synthesis. P binds to albumin and Corticosteroid Binding Globulin (CBG) at a rate of ~4:1. Androgen Binding Protein (ABP)are produced by the Sertoli cells under stimulation by FSH and T. It keeps high levels of T near sperm maturing in the rete testis and epididymis.

What are the types of peptide hormones involved in the Hypothalamic-Pituitary-Gonadal Axis? What do they do? Inhibins and Activins.Inhibins are made by FSH stimulated Sertoli or Granulosa cells and act on the anterior pituitary to decrease FSH release. Come in two forms αβ(a) and αβ(b) called inhibin A and inhibin B, respectfully. They act on the AP to decrease FSH release. Inhibin B is made in the male and during the follicular phase in the female, but inhibin A is only characteristic of the luteal phase. Activins are formed from two inhibin β chains. Can be either homo (β(a)β(a) β(b)β(b)) or heterodimers (β(a)β(b)). Function is not yet known, but increased dramatically before birth.

What are the three types of sex definitions? Genetic (karyotype), Gonadal (internal genitalia), and Phenotypic (genital ducts, external genitalia, and secondary sexual characteristics)

What is the definition in terms of Genetic Sex? Defined by the karyotype where there are 44 somatic chromosomes plus either XX for females or XY for males.

What is the definition of Gonadal sex? Gonadal sex is defined by the internal genitalia. Is inherent in the genetic makeup. Downstream action of the SRY (Sex-determining Region of Y) gene product induces testis development. Both X's are required for normal ovarian development, although later only one remains active.

What is the definition of Phenotypic sex? How do the male/female parts develop? Phenotypic sex if defined by the genital ducts, external genitalia, and secondary sexual characteristics. In the male, Sertoli cells produce Mullerian Inhibiting Hormone (MIH) that causes regression of the Mullerian ducts. The Mullerian ducts are the precursor of the oviducts, uterus, and vagina. The Leydig cells produce testosterone which supports differentiation of the Wolffian ducts (which is a precursor of the epididymis, vas deferens, seminal vesicle, and ejaculatory duct). The testosterone, after it gets converted to DHT, it induces development of the prostate, urethra, penis, and scrotum. Since the females lack MIH and testosterone, the Mullerian ducts develop and the Wolffian ducts regress. In either sex, fetal steroidogenesis is supported by hCG.

What is Turner's syndrome? Also called ovarian agenesis; XO - individual lacking secondary sexual characteristics.

What is Kleinfelter's syndrome? Also called seminiferous tubule dysgenesis. XXY. Has male genitalia, but also feminization. Example of Hypergonadotropic hypogonadism. High FSH, LH, and E2, but low T.

What is the Triple X syndrome? XXX - no unusual abnormalities since only one X chromosome remains active.

Describe the unique male sexual development. Testosterone is synthesized near adult levels at the end of the first trimester (leads of differentiation of internal and external genitalia) and again 2 months postpartum. (reason unknown) The level remains low until puberty at which point the hypothalamus becomes active and increasing testosterone levels. This causes growth of the penis, sebaceous glands, long bones, and axillary/pubic hair. Testosterone reaches it max concentration during the mid/late 20s and then falls gradually afterwards.

Describe the unique female sexual development. Estrogen synthesis is seen during gonadal development towards the end of the first trimester and FSH/LH are high 2-3 months postpartum. (reason unknown) Estrogen levels do not rise again until puberty, where the first defining event is breast development (thelarche) followed by development of the axillary/pubic hair (pubarche), and finally the first menstrual period (menarche). Estrogen levels peak monthy after menarche (except during pregnancy), then after awhile periods become irregular (climacteric) and cease around the fifth decade (menopause). Post-menopausal LH and FSH levels are high due to low estrogen and lack of inhibin.

Describe the common sexual development between males and females. In both sexes, the long bone growth is augmented by sex steroids (E in females; T -> E in males by aromatase) but high levels of sex steroids near the end of puberty bring about the end of long bone growth by epiphyseal plate closure. At 8-10 years, adrenals increase their secretion of androgens (adrenarche), without significant changes in cortisol or ACTH levels. These androgens (from androstedione) contribute to the early stages of the growth spurt and to pubic/axillary hair growth, independent of gonadal puberty.

What is Testicular Feminization? Also called androgen insensitivity syndrome. XY genotype but has female external genitalia. This is caused by having no functional androgen receptors. Y chromosome makes the testis, which make MIH and testosterone. MIH cause Mullerian ducts to regress, but Wolffian ducts can't be stimulated because they can't respond to testosterone. Sertoli cells can't nurse sperm so no spermatogenesis due to lack of ducts. Later on, without negative feedback from T, due to no receptors, GnRH increases => LH increases => A increases => T increases => E increases due to peripheral aromatization => breast development => female phenotype even though levels of T > E.

What is 5α-reductase-2 Deficiency Syndrome? Also called penis at twelve syndrome. XY genotype. Starts life with a female phenotype, but reverts later to a male phenotype. Caused by one of the two 5α-reductase genes (type 2) being nonfunctional. The Y chromosome makes testes, which secrete T. This will a start differentiation of the Wolffian ducts and the internal male ducts are present, but no prostate, penis, or scrotum due to the conversion of DHT being required for this. At puberty, with high T and/or normal 5α-reductase type 1 in the prostate will cause development of the external male genitalia.

What is Congenital Adrenal Hyperplasia (CAH)? In females, this causes masculinization where there is enlargement of the clitoris and fusion of the labia before birth. This causes increased muscular development, facial hair (hirsuitism), irregular menses post puberty. In males, this causes precocious puberty or super-masculinization. This is caused by hypersecretion of adrenal androgens due to a defect in steroid biosynthesis. Most commonly a 21- or 11β- hydroxylase deficiency reduces the formation of aldosterone and cortisol, resulting in in accumulation of their androgen precursors. (estrogen/testosterone)