Ovarian steroid production in a woman with polycystic ovary syndrome associated with endometrial cancer.

A young woman with typical polycystic ovary syndrome (PCO) underwent laparotomy for moderately differentiated endometrial cancer. Specimens from the hyperplastic thecal and stromal tissue of the ovaries were incubated for 2 hours in the presence or absence of hCG, 100 IU/ml. Following incubation the tissue content of cyclic AMP and the amounts of progesterone (P), androstenedione (A), testosterone (T) and estradiol-17 beta (E2) in the incubation medium were analysed. For comparison, thecal cells from normal ovaries of regularly menstruating women were incubated under identical conditions. In vivo, the PCO ovaries secreted several-fold greater amounts of T than normal ovaries. In vitro, the thecal cells were much more active, steroidogenically, than the stromal cells of the PCO ovary. Furthermore, the hyperplastic thecal cells of the PCO ovary produced several-fold greater amounts of androgens, and appeared more sensitive to stimulation with hCG, as compared with thecal cells from normal ovaries. The results indicate that in women with PCO associated with endometrial cancer the hyperplastic thecal cells are a significant site of abnormal androgen production and abnormal sensitivity to gonadotropin.

Influence of human chorionic gonadotropin in vivo on steroid formation and gonadotropin responsiveness of isolated human preovulatory follicular cells.

Granulosa and thecal cells of preovulatory follicles taken from 12 women were isolated and incubated separately for 2 hours in the presence and absence of human chorionic gonadotropin (hCG). To six of these women, an ovulatory dose of hCG (9000 IU) had been given 24 to 30 hours before excision of the follicle. Following incubation, cellular cyclic adenosine 3':5' monophosphate (cAMP) levels and the medium content of progesterone (P), androstenedione (A), and 17 beta-estradiol (E2) were determined. All follicles appeared healthy and well developed, and the oocytes recovered were morphologically normal and mature. Exposure to hCG in vivo caused a shift in steroidogenesis from A toward P formation in isolated thecal cells and a marked increase in the P production by the granulosa cells of the preovulatory follicles. Furthermore, the thecal cells, but not the granulosa cells, developed refractoriness to further stimulation with hCG in vitro.

Progesterone and adenosine 3',5'-monophosphate formation by isolated human corpora lutea of different ages: influences of human chorionic gonadotropin and prostaglandins.

From each of 24 women undergoing minilaparotomy at various stages of the luteal phase of the cycle, the corpus luteum (CL) was excised in toto, decapsulated, cut into pieces, and incubated for short time periods (5--120 min). Incubations were carried out in the absence and presence of hCG, prostaglandin F2 alpha (PGF2 alpha) and PGE2, both alone and in combination. Dating of the CL was done meticulously using several parameters. After incubation, the tissue levels of cAMP and the media concentrations of progesterone (P) were determined. The basal P production in vitro was highest in CL of the midluteal phase. hCG stimulated cAMP formation in CL of all ages, with the highest levels of cAMP being produced in CL of the midluteal phase. PGE2 was found to increase cAMP formation and potentiate the hCG effect in young CL, but not in CL of the midluteal phase. PGF2 alpha, alone or in combination with hCG, had no effect on cAMP or P formation in either young or old CL, while in CL of the midluteal phase, PGF2 alpha significantly counteracted the stimulatory effect of hCG on both cAMP and P formation. These in vitro data show that PGF2 alpha is capable of inducing functional luteolysis in humans.

Steroid and adenosine 3',5'-monophosphate formation in granulosa and thecal cells from human preovulatory follicles in response to human chorionic gonadotropin.

Granulosa and thecal cells from the preovulatory follicles of 14 women were mechanically isolated and separately incubated for short term periods (0.5-4 h) in the presence and absence of hCG. After incubation, tissue cAMP levels and medium progesterone content of (P), androstenedione (A), and 17 beta-estradiol (E2) were determined. All follicles appeared healthy and mature, as judged by their number of granulosa cells, histological examination of the oocytes, athe steroid levels in antral fluid, as well as the appearance of the oocyte-cumulus complexes. Under basal conditions, both granulosa and thecal cells had the capacity to synthesize all of the steroids measured. The predominant steroid formed by the granulosa cells was P, while the thecal cells formed A as the major steroid. Both cell types produced considerable amounts of E2. The addition of hCG in various concentrations gave rise to concentration-dependent increase in cAMP formation in both cell types. Furthermore, hCG caused a statistically significant increase in the formation of P and A by the thecal cells, while steroid formation by the granulosa cells was not significantly altered. With higher concentrations of hCG, however, there was a tendency toward a stimulation of P synthesis in the granulosa cells from most of the follicles tested. It is concluded that in preovulatory follicles of human origin, follicular steroidogenesis is not rigidly compartmentalized between the two cell types. Furthermore, both granulosa and thecal cells are sensitive to stimulation with hCG in this type of follicle.

Hilus cells from human postmenopausal ovaries: gonadotrophin sensitivity, steroid and cyclic AMP production.

Strips of ovarian hilar tissue taken from 11 post-menopausal women were examined histologically and found to contain clusters of hilus cells in contiguity with non-myelinated nerve fibers. No other steroidogenically active structures were found. Specimens from these strips were incubated for 30 and 240 minutes in Krebs bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. The specimens produced measureable amounts of androstenedione, estradiol-17 beta and progesterone in vitro. The major steroid formed was androstenedione, and this pattern of steroidogenesis appeared similar to that of postmenopausal ovarian stroma. However, the amounts of steroids formed were considerably higher than in stromal tissue. This implies that the hilus cells possibly may be of greater importance, qualitatively, than the stroma cells for steroidogenesis in the postmenopausal ovary. Addition of hCG to the incubated specimens elicited increase in both cyclic AMP formation and steroid synthesis, especially of estradiol-17 beta, indicating a preserved responsiveness to gonadotrophin in hilus cells from postmenopasual ovaries.

Steroid production and responsiveness to gonadotropin and prostaglandins of human ovarian follicles at term pregnancy.

PIP: This article was undertaken to correlate the steroidogenic capacity of human follicles in later pregnancy to their histological appearance. Specimens for the study were obtained from the ovaries of 26 women undergoing elective cesarean section. Human chorionic gonadotropin did not influence follicular production of cyclic AMP (adenosine monophosophate) and steroids in vitro. However, prostaglandin E2 and F2 alpha did elicit a stimulating effect on the follicular cyclic AMP system, thus indicating a well-preserved adenylate cyclase system in spite of morphologic signs of early atresia.^ieng

Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries.

Specimens from the ovarian cortical stroma of 15 postmenopausal women were examined histologically and were incubated for 4 hours in Krebs' bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. Specimens of normal postmenopausal stroma produced measurable amounts of androstenedione, estradiol, and progesterone in vitro. Specimens with stromal hyperplasia produced larger amounts of androstenedione and estradiol than those with normal stroma. Androstenedione was the predominant steroid produced in both groups. The nonnegligible formation of estradiol indicated an aromatizing capacity of the stromal tissue. The addition of hCG elicited a significant increase in cyclic AMP formation in specimens from ovaries with stromal hyperplasia, indicating a preserved responsiveness to gonadotropin in this type of ovaries.