M.J. Jawad

Suppression of human chorionic gonadotropin by progestational steroids

The dynamics of the secretion of human chorionic gonadotropin (hCG) were studied by culturing explants of normal term placentas for as long as 144 hours. A significant accumulation of immunoreactive hCG (beta-subunit) was first detected at 48 to 72 hours, and a sixfold increase in hCG was observed in control culture medium at 144 hours. Compared to control cultures, progesterone (P < 0.001) in physiologic tissue levels of 5 to 20 micrograms/ml, pregnenolone (P < 0.001), 20 micrograms/ml, and 20 alpha-dihydroprogesterone (P < 0.001), 20 micrograms/ml, suppressed the secretion of hCG throughout the study period. Progesterone decreased the secretion of hCG in a dose-response manner (r = -0.8S87, P < 0.1). No suppression of hCG was observed in the presence of cortisol, testosterone, dihydrotestosterone, 17 beta-estradiol, or estriol. The secretion of human chorionic somatomammotropin was unchanged in the presence of progesterone. The augmented hCG response in the presence of dibutyl cAMP (P < 0.001) was significantly, but not completely, suppressed by progesterone 20 micrograms/ml culture medium (P < 0.01). Under these conditions progestational steroids or their immediate metabolites suppress the secretion of hCG, and they may be responsible for the decline in the levels of hCG during pregnancy.

Prolactin hyperstimulation in response to thyrotropin-releasing hormone in patients with endometriosis

In order to clarify the role of hyperprolactinemia as a possible cause of infertility in patients with endometriosis, baseline serum prolactin (PRL) concentrations and the PRL response to thyrotropin-releasing hormone (TRH) stimulation were measured in 14 infertile women with endometriosis and in 13 normal, fertile women. Baseline PRL concentrations were 2-fold greater in the endometriosis group than in normal subjects, but the mean values did not differ significantly. Following TRH administration, a significant increase in peak PRL concentrations was observed in patients with endometriosis (211.5 +/- 34.9 ng/ml) when compared with corresponding values in control subjects (117.1 +/- 14.9 ng/ml, P less than 0.05). This hypersecretory state was selective for PRL because no significant differences between the baseline and TRH-stimulated thyroid-stimulating hormone (TSH) concentrations or total serum thyroxine concentrations were observed. In summary, some infertile women with endometriosis exhibit a greater capacity for PRL secretion than normal women. These results suggest that relative hyperprolactinemia may be responsible for the infertility associated with endometriosis, and that PRL suppression may be indicated in these patients.

Effect of estradiol and progesterone on human chorionic gonadotropin secretion in vitro

Many of the substances known to control the secretion of pituitary gonadotropins also modulate the secretion of human chorionic gonadotropin (hCG) by the placenta. In order to study the effect of estrogens and progestins on hCG secretion, term placental explants were cultured in culture media for 144 hours. During the culture period, hCG secretion increased after 48 hours, and a fortyfold increase was observed after 144 hours (p less than 0.001). Compared to concentrations of hCG in control cultures, secretion of hCG was markedly suppressed in the presence of progesterone 2.25 X 10(-5)M (p less than 0.001), a concentration similar to that found in term placental tissue (1.7 +/- 0.2 micrograms/gm of tissue). Suppression of hCG by progesterone occurred in a dose-response manner (r = -0.9100, p less than 0.01). Estradiol, an important steroid modulator of pituitary gonadotropins, did not significantly suppress the secretion of hCG, except in pharmacologic concentrations (10(-4)M), and physiologic concentrations of estradiol had no effect on the suppression of hCG by progesterone. These results suggest that the mechanism by which progesterone suppresses the secretion of hCG differs from the manner in which steroids modulate the secretion of pituitary gonadotropins.

Effect of dextran-coated charcoal on radioimmunoassays of unconjugated estriol in serum

Lipid interference in the radioimmunoassay of steroids can cause an apparent variation in post-prandial serum concentrations of unconjugated estriol. The effects of increased concentrations of dextran-coated charcoal (15--60 g/l) in the radioimmunoassay of estriol standards with and without triglycerides were studied. All concentrations of dextran-coated charcoal used in this study eliminated the previously observed effects of estriol-lipid partitioning. When we used similar concentrations of dextran-coated charcoal, we found that serum cortisol levels in pregnant women declined significantly during the day (P less than 0.001), but no significant variation in estriol concentrations was observed. These results indicate that the previously reported diurnal variation in serum unconjugated estriol concentrations attributed to steroid-lipid partitioning can be eliminated by increasing the concentration of dextran-coated charcoal in assays using this method of separation.

Corticosteroid-binding globulin as a biologic assay for endogenous estrogen in patients with and without endometrial carcinoma

Serum corticosteroid-binding globulin (CBG) concentrations in blood respond to endogenous or exogenous estrogens in a dose-response manner and serve as a biologic assay for estrogens. Because endometrial carcinoma is associated with unopposed or excessive estrogen stimulation, the CBG binding capacity of sera of patients with endometrial cancer was compared to that of normal premenopausal and postmenopausal women. The mean +/- SEM values for CBG concentrations in patients with endometrial cancer (28.3 +/- 1.3 mg/L) were significantly greater than CBG concentrations in premenopausal women (21.4 +/- 0.9 mg/L, p less than 0.001), but not significantly different from those of normal postmenopausal women (26.7 +/- 1.2 mg/L). Patients with polycystic ovarian disease, a risk factor for endometrial carcinoma, also had CBG concentrations significantly greater than those of normal premenopausal women (27.9 +/- 1.8 mg/L, p less than 0.01). CBG levels decline with age (r = -0.6474, p less than 0.05) but are unaffected by body weight or percent ideal body weight. These results indicate that CBG can distinguish categories of patients at risk for endometrial carcinoma, but it is not an effective biochemical marker for patients in these high-risk groups who have or will develop endometrial carcinoma.