Publisher Summary This chapter presents an overview of the regulation of the mammalian corpus luteum (CL) The CL is an ovarian follicle in which the rapid regression—that is otherwise the fate of all postovulatory follicles—is temporarily arrested In the mammalian CL, progesterone secretion goes hand in hand with the postponement of regression It is fairly certain that reptilian CL also secretes progesterone The mammalian CL is formed during the period around ovulation by a transformation of the cells lining the cavity of the follicle Luteinization affects the granulosa cells in all species It involves an enormous enlargement of the cell with a great increase in the nucleus–cytoplasm ratio and the formation of a very distinct cell wall, the development of an extensive capillary network enmeshing all the cells, a marked proliferation of the endoplasmic reticulum, and its transformation from a predominantly rough to a predominantly smooth type, a marked proliferation of the mitochondria from a small round or rod shape type with lamelliform cristae into larger and more varied shapes with tubular and villiform cristae, and an increase in the complexity of the Golgi apparatus The CLs activity differs most from that of the follicle in how much rather than in what kinds of steroid it makes The principal change is a striking increase in progesterone secretion, accompanied by a variable, but severe fall or even loss of the capacity for estrogen and androgen secretion

The Regulation of the Mammalian Corpus Luteum

The concentrations of steroids in antral fluid, the number of granulosa cells, the status of the oocyte, and the diameter of each follicle were determined in human ovaries so that follicles at each stage of the menstrual cycle could be classified as large (>8 mm diameter) or small (<8 mm diameter) and healthy or atretic. The granulosa cells and thecal-enriched tissue from each follicle and the stromal tissue from each ovary were cultured for 6 days in vitro. The amounts of progesterone (P), androstenedione (Δ4), testosterone, dihydrotestosterone, es-trone, and estradiol (E2) generated by the different tissues were measured on days 0, 2, 4, and 6 of culture. It was found that granulosa cells, thecal tissue, and stromal tissue all have the biosynthetic capacity to produce (P, Δ4 (,)tes -tosterone, dihydrotestosterone, estrone, and (E2No individual steroid-secreting compartment of the ovaries studied, whether part of the follicle or of the stroma, had the exclusive capability of producing any of the above-na...

The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro.

Background The aspiration of the granulosa cells that surround the oocyte and the use of gonadotropin releasing hormone agonists (GnRHa) during assisted reproduction technology (ART) treatment can interfere with the production, during the luteal phase, of progesterone, which is necessary for successful implantation of the embryo. Providing hormonal supplementation during the luteal phase with either progesterone itself, or human chorionic gonadotropin (hCG), which stimulates progesterone production, may improve implantation and, thus, pregnancy rates. Objectives To determine (1) if luteal phase support after assisted reproduction increases the pregnancy rate, (2) the optimal hormone for luteal phase support, i.e. hCG, progesterone, or a combination of both, and (3) the optimal route of progesterone administration. Search strategy We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1971 to Dec 2003), EMBASE (1985 to Dec 2003). We handsearched reference lists of relevant articles were scanned, and abstract books from scientific meetings up to December 2003. Selection criteria Randomized controlled trials of luteal phase support after ART treatment, comparing hCG or progesterone with placebo or no treatment, comparing progesterone with hCG, progesterone plus hCG, or progesterone plus estrogen, or comparing different routes of progesterone administration. Quasi-randomized trials were excluded from the main analyses, but included in a secondary analysis for each comparison. Data collection and analysis For each comparison, data on live birth, ongoing and clinical pregnancy per embryo or gamete transfer procedure, miscarriage per clinical pregnancy, ovarian hyperstimulation syndrome (OHSS) per transfer, and multiple pregnancy per clinical pregnancy were extracted into 2 x 2 tables and subgrouped by use of GnRHa in the ovarian stimulation regimen. The odds ratio (OR) and risk difference (RD) were calculated. Main results Fifty-nine studies were included in the review. Luteal phase support with hCG provided significant benefit, compared to placebo or no treatment, in terms of increased ongoing pregnancy rates (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.32 to 4.29) and decreased miscarriage rates (OR 0.12, 95% CI 0.03 to 0.50), but only when GnRHa was used. The odds of OHSS increased 20-fold when hCG was used in cycles with GnRHa. Progesterone use resulted in a small but significant increase in pregnancy rates (OR 1.34, 95% CI 1.01 to 1.79) when trials with and without GnRHa were grouped together, but no effect on the miscarriage rate was observed. No significant difference was found between progesterone and hCG or between progesterone and progesterone plus hCG or estrogen in terms of pregnancy or miscarriage rates, but the odds of OHSS were more than 2-fold higher with treatments involving hCG than with progesterone alone(OR 3.06, 95% CI 1.59 to 5.86). Comparing routes of progesterone administration, reductions in clinical pregnancy rate with the oral route, compared to the intramuscular or vaginal routes, did not reach statistical significance, but there was evidence of benefit of the intramuscular over the vaginal route for the outcomes of ongoing pregnancy and live birth. No significant difference in pregnancy rate was observed between vaginal progesterone gel and other types of vaginal progesterone. Reviewers' conclusions Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate. hCG does not provide better results than progesterone, and is associated with a greater risk of OHSS when used with GnRHa. The optimal route of progesterone administration has not yet been established.

Luteal phase support in assisted reproduction cycles

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders in which there is a deficiency of one of the enzymes necessary for cortisol synthesis. An abnormality in each of the enzymatic activities required for cortisol synthesis has been described. As a result of the disordered enzymatic step, there is decreased cortisol synthesis, increased ACTH via a negative feedback system, overproduction of the hormones prior to the enzymatic step or not requiring the deficient enzyme, and deficiency of the hormones distal to the disordered enzymatic step. Since several of the enzymatic steps are required for sex hormone synthesis by the gonad, a disordered enzymatic step in the gonad resulting in gonadal steroid hormone deficiency may also be present. This chapter presents an overview of all of the enzymatic deficiencies resulting in CAH with the most extensive review of 21-hydroxylase deficiency which is the most common, first described, and most intensively studied of the enzymatic disorders.

https://www.nejm.org/doi/pdf/10.1056/NEJMra021561

Congenital adrenal hyperplasia

Publisher Summary Early in fetal life there is relatively autonomous secretion of hypothalamic hypophysiotropic releasing factors and later in development the maturation of inhibitory or restraining influences, mediated via the central nervous system (CNS), modulates pituitary secretion. Even at birth, CNS regulation of pituitary function is incomplete. Therefore, the maturation of CNS control of anterior hypophysial function can be looked upon as a continuum, extending from fetal life into a variable period in infancy and in relation to gonadotropin secretion, into adolescence. This chapter emphasizes on the limitations of measuring pituitary content and serum concentration of hormones in human fetuses obtained largely after therapeutic abortion. It also provides an overview of some of the factors that can influence the plasma concentration of pituitary hormones. The chapter discusses the morphological changes in the hypothalamic-pituitary complex in the fetus, human fetal hypothalamic-hypophysiotropic factors, hypothalamic content and concentration of releasing factors in human fetuses, human fetal pituitary hormones, placental polypeptide hormones, and pituitary hormones in anencephaly. The developmental pattern of secretion of fetal pituitary hormones is not only diverse, but the hormones apparently develop independently of each other.

The ontogenesis of pituitary hormones and hypothalamic factors in the human fetus: maturation of central nervous system regulation of anterior pituitary function.

Slices of stromal tissue from 8 normal human ovaries, obtained at different stages of the menstrual cycle and pregnancy, were incubated in vitro in the presence of acetate-1-14C. The radioactive steroids formed were identified by reverse isotope dilution and radiochemical purity was established by crystallization to constant specific activity. The biosynthesis of Δ4-androstene-3,17-dione, testosterone, 3β-hydroxy-,Δ5-androsten-17-one, 17-hydroxy-Δ4-pregnene-3,20-dione, 3β-hydroxy-Δ5-pregnen-20-one, estrone and estradiol-17β was demonstrated. Little or no radioactive progesterone was found. Radioactive androgens were the major group of steroids found in all incubations. The highest incorporations of acetate-l-14C into steroids were found with those normal ovarian specimens obtained early in the luteal phase of the menstrual cycle and during pregnancy. Radioactive steroid synthesis could be augmented in certain instances by human chorionic gonadotropin and by preparations of human pituitary gonadotropins. O...

Steroid hormone formation in the human ovary. IV. Ovarian stromal compartment; formation of radioactive steroids from acetate-1-14C and action of gonadotropins.

Steroidogenesis in human corpora lutea obtained from women during the luteal phase of the menstrual cycle and from women with ectopic pregnancy is stimulated by the addition in vitro of hormones of human origin with luteinizing action. Human chorionic gonadotropin and human pituitary luteinizing hormone (LH) were active; no effect was observed with ovine luteinizing hormone or prolactin. The stimulation of steroidogenesis was assessed by the increase in incorporation of acetate-1-14C into progesterone, 20α-hydroxy-Δ4-pregnen-3-one, 17-hydroxyprogesterone, Δ4-androstene-3,17-dione, estradiol-17β and estrone. The corpora lutea from ectopic pregnancy showed a higher incorporation of radioactivity into all steroids than corpora lutea of the menstrual cycle.

Steroid hormone formation in the human ovary. ii. action of gonadotropins in vitro in the corpus luteum.

Slices of 6 human corpora lutea of the menstrual cycle and ectopic pregnancy were incubated in vitro in the presence of acetate-1-14C. By means of carrier dilution and stringent purification measures, the biosynthesis of 7 radioactive steroids has been demonstrated in the 2 types of corpora lutea. These steroids include progesterone, 20α-hydroxy-Δ4-pregnen-3-one, 17-hydroxyprogesterone, Δ4-androstene-3,17-dione, estradiol-17β, estrone and pregnenolone (3β-hydroxy-Δ5-pregnen-20-one). Quantitative measures of incorporation of radioactivity in these tissues indicate progesterone to be the major steroid formed in vitro in the human corpus luteum.

Steroid hormone formation in the human ovary. i. identification of steroids formed in vitro from acetate-1-14c in the corpus luteum.

The gonadotropin receptor of the human corpus luteum

Progesterone synthesis in vitro and the influence of exogenous gonadotropin were studied in slices of 50 individual human corpora lutea removed at different times during the reproductive cycle. Radioactive progesterone synthesis (dpm) was assessed by incorporation of radioactivity from acetate-1-14C. The progesterone contained in corpora lutea and formed in vitro from endogenous precursors (μg) was measured spectrophotometrically by its absorption of ultraviolet light. All luteal phase corpora lutea synthesized progesterone in vitro as measured by these 2 parameters (dpm and μg). No radioactive progesterone synthesis (dpm) from acetate-1-l4C was found in 3 corpora lutea obtained after onset of menses, although 2 of the 3 specimens synthesized progesterone (μg) from endogenous precursors. Corpora lutea from all phases of pregnancy and up to 4 days post partum synthesized progesterone in vitro. The capacity for steroid biosynthesis during the post-par turn period appeared to decline gradually when ...

Bernard F. Rice

Papers

Steroid hormone formation in the human ovary. IV. Ovarian stromal compartment; formation of radioactive steroids from acetate-1-14C and action of gonadotropins.

Steroid hormone formation in the human ovary. ii. action of gonadotropins in vitro in the corpus luteum.

Steroid hormone formation in the human ovary. i. identification of steroids formed in vitro from acetate-1-14c in the corpus luteum.

The gonadotropin receptor of the human corpus luteum

Steroid Hormone Formation in the Human Ovary: V. Synthesis of Progesterone in Vitro in Corpora Lute a During the Reproductive Cycle