Deprivation and repletion of androgen in vivo modifies triacylglycerol synthesis by rat hepatocytes.

Given the same quantity of fatty acid, livers from male rats esterify less fatty acid and secrete less triacylglycerol in very-low-density lipoprotein than do livers from female animals. To elucidate the role of testosterone in maintenance of this male pattern, conversion of [1-14C]oleic acid into triacylglycerol was assessed in vitro by rat hepatocytes (male) following gonadectomy and replacement with testosterone. Following castration, incorporation of fatty acid into triacylglycerol was increased. In contrast, esterification of exogenous fatty acid into phospholipid, cholesteryl esters, and diacylglycerol was unchanged. Treatment with testosterone (75 micrograms/day) reduced incorporation of exogenous fatty acid into triacylglycerol. Higher doses of testosterone (200 or 100 micrograms/day) modified the effect, such that inhibition was observed only at low oleate (0.5 mM) concentrations. At higher substrate concentrations (1.0-2.0 mM) the inhibitory effect was no longer observed. Further, a similar dose-dependent effect of testosterone was observed following in vivo treatment of castrate females with testosterone. These data support the concept of a regulatory role of testosterone in hepatic triacylglycerol synthesis. These findings also demonstrate a biphasic effect of testosterone, an effect that is dependent not only upon the dose of testosterone administered, but also on the concentration of fatty acid to which the hepatocyte is exposed in vitro.

The effect of leupeptin on progestin receptors of human uterine tissues.

In preparation for studies of progestin receptor dynamics in human uterine tissues, we have investigated the effect of tissue handling and the protease inhibitor leupeptin on the molecular forms of progestin receptors in human endometrium, myometrium, and leiomyoma. Tritiated R5020 [17,21-dimethyl-19-nor-4,9-pregnadiene-3.20-dione) (promegestone)] was the labeled ligand, and sucrose density gradient ultracentrifugation was used to determine the sedimentation coefficients of the receptors. Scatchard plots of saturation analyses were used to determine the number of binding sites and dissociation constants. We found that rapid chilling of tissue at surgery was necessary to maintain specific progestin binding in myometrium, that leupeptin permitted demonstration of 8S receptors in myometrium and leiomyoma, and that 8S receptors were present in endometrium, with or without leupeptin. With careful handling of tissue and minimal homogenization, leupeptin may not be necessary to preserve 8S receptors in myometrium and leiomyoma cytosols; however, the use of leupeptin gives greater assurance that 8S receptors will be preserved. The number of binding sites varied from 0.6-2.0 pmol/mg cytosol protein, and the Kd values observed were between 1.7-6.9 X 10(-10) M.

beta-Endorphin and beta-lipotropin plasma levels in hirsute women: correlation with body weight.

Based on the findings of elevated circulating beta-endorphin (beta-END) levels in genetically obese (fa/fa) fats and the reversal of the overeating of genetically obese (ob/ob) mice by naloxone, circulating beta-END and beta-lipotropin (beta-LPH) levels were measured in 8 hirsute, hyperandrogenic, oligo-amenorrheic women of varying weights. Circulating beta-END and beta-LPH levels were significantly elevated (p less than .001) above the levels in nonobese control subjects and were positively correlated with body weight (p less than .025). Based on these data and indirect evidence in the literature, we propose a role may exist for beta-END and/or beta-LPH in human obesity and in adrenal androgen secretion.

Deficient 17 beta-hydroxysteroid oxidoreductase activity in testes from a male pseudohermaphrodite.

17beta-Hydroxysteroid oxidoreductase (17 beta-HOR) activity in testicular tissue from a male pseudohermaphrodite (MP) who had elevated plasma LH and androstenedione (A) levels, and normal dehydroepiandrosterone (DHA) levels was compared by in vitro studies to that of testicular tissue from a normal man. The 17 beta-HOR activity from the MP was localized predominantly in the microsomal fraction, as it is in normal testicular tissue. With DHA, A, and estrone as substrates, the 17 beta-HOR activity of the MP was decreased in the presence of NADPH, but not NADH, in comparison with the normal. NADPH was the preferred co-factor for 17 beta-HOR from the normal testes, while 17 beta-HOR activity from the MP testes was less with NADPH than with NADH as cofactor. These results indicate that the inefficient testosterone production in the MP testes may be accounted for by a deficiency of NADPH-dependent 17 beta-HOR activity. Further studies suggested that 3 beta-hydroxysteroid oxidoreductase-isomerase (3 beta-HOR) was increased in the MP testes and was much greater than 17 beta-HOR activity with DHA as substrate. These findings largely explain the elevated plasma A levels with normal DHA levels, and suggest that DHA leads to A leads to testosterone was the major route of testosterone biosynthesis in the MP testes.

A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.

UNLABELLED: A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. CONCLUSIONS: 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.

Adrenal function in hirsutism I. Diurnal change and response of plasma androstenedione, testosterone, 17-hydroxyprogesterone, cortisol, LH and FSH to dexamethasone and 1/2 unit of ACTH.

ACTH dependency of plasma androstenedione (A) and testosterone (T) was determined in normal and hirsute women by measuring the magnitude of change of A and T between the time of the cortisol (F) peak and F nadir in a diurnal study. There was a significant diurnal rhythm of A synchronous with F in both normal and hirsute women (P less than 0.01). Five of 12 hirsute women had a greater than normal diurnal swing of A (P less than 0.05), but only 2 of the 12 had a greater than normal diurnal swing of T. Responsiveness of A and T to 1/2 unit of intravenous ACTH was determined after dexamethasone 1 mg was given the night before. Plasma A and T were elevated in most of the hirsute women during acute ACTH suppression by dexamethasone, indicating ACTH-independent hypersecretion of androgens. Nine of 17 hirsute women had a greater than normal A response to ACTH (P less than 0.05). Those who had an exaggerated diurnal swing of A also had hyper-responsiveness of A secretion to ACTH. Only 2 hirsute women had an exaggerated T response to ACTH. Some T levels were decreased by ACTH. Seven of the 9 hiruste women who had an exaggerated A response to ACTH had a normal maximum F response, but a greater than normal 17-hydroxy-progesterone (17-OHP) response to ACTH with a high 17-OHP to F ratio, suggesting they have a mild but compensated reduction in 21-hydroxylase or 11beta-hydroxylase activity. Two women with hyper-responsiveness of A secretion had low F and 17-OHP responses to ACTH suggesting reduced C21 but intact C19 3beta-hydroxysteroid dehydrogenase-delta-5,-4 isomerase activity. These apparent reduced enzyme activity may not be congenital, but induced by an altered hormonal milieu such as an abnormal androgen-estrogen ratio. It is concluded that ACTH uniformly stimulated A secretion but not T secretion and that approximately 50% of the hirsute women had ACTH-dependent hypersecretion of A, but most of these also had concurrent ACTH-independent hypersecretion of androgens.

Human ovarian 17 beta-hydroxysteroid oxidoreductase activity: a comparison of normal and polycystic ovarian tissues.

Ovarian tissue and ovarian venous blood were obtained from women undergoing wedge resection, and ovarian tissue was obtained from normally menstruating women who had an oophorectomy for medical reasons. A morphological evaluation was made of the wedged tissue. 17 beta-Hydroxysteroid oxidoreductase levels were determined as the 17-ketoreductase (17-KR) and 17 beta-dehydrogenase activities in both normal and wedged tissue. Plasma androstenedione (A) and testosterone (T) levels were measured in the ovarian venous blood. Low, but measurable, 17 beta-hydroxysteroid oxidoreductase activity was found in the mitochondria, microsomes, and cytosol. With whole, cell-free homogenates, mean 17-KR activity was not significantly different in normal tissues and polycystic tissues; mean 17-KR activity of corpora lutea was significantly greater than that of the other tissues. Mean 17 beta-dehydrogenase activity was not significantly different from 17-KR activity in the tissues studied. Ovarian venous A levels were higher than the reported mean ovarian venous A levels of normal women with only one exception; approximately half of the ovarian venous T levels were higher than reported mean ovarian venous T levels of normal women. The morphology of the wedge sections did not correlate well with the biochemical data.

The effects of continuous androgen secretion on the hypothalamic-pituitary axis in woman: evidence from a luteinized thecoma of the ovary.

Hyperandrogenic states in women are often accompanied by disruption of gonadotropin secretion. However, the role of androgens per se in the pathogenesis of this abnormality is poorly understood. We report a woman with a virilizing ovarian tumor in whom the effects of continuous androgen secretion on the hypothalamic-pituitary axis were investigated in detail. A 29-yr-old woman with previously normal reproductive function, including prior fertility, was evaluated for amenorrhea and hirsutism. She had elevated peripheral serum levels of testosterone (T; 337-500 ng/dl) and androstenedione (A; 258-353 ng/dl). Her serum LH level was above the normal follicular phase range and was hyperresponsive to LHRH, whereas the FSH level was below normal early follicular phase levels and increased minimally in response to LHRH. A luteinized thecoma of the left ovary, shown by catherization of the ovarian venous blood to be secreting both T and A, was removed. Postoperatively, serum T and A levels returned to normal, and the patient had a normal ovulatory menstrual cycle in the 30 days after the operation, documented by daily determinations of plasma estradiol, progesterone, and gonadotropin levels. A repeat LHRH test in the follicular phase of the second postoperative menstrual cycle was completely normal. This case indicates that the characteristic abnormalities of gonadotropin secretion observed in hyperandrogenic states such as polycystic ovarian disease can result from chronic androgen secretion by an ovarian tumor and that normal folliculogenesis and gonadotropin secretion can be promptly restored by the elimination of the androgen excess.

Mechanisms of insulin inhibition of ACTH-stimulated steroid secretion by cultured bovine adrenocortical cells.

Results of previous studies indicated that insulin at levels comparable to those in humans during hyperinsulinemia decreased ACTH-stimulated cortisol and androstenedione secretion by bovine adrenal fasciculata-reticularis cells in primary culture. In the present studies this inhibitory action was examined further by comparing the effects of insulin on ACTH-stimulated corticosteroid secretion with its effects on 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), forskolin- and [5val]angiotensin II (Ang II)-stimulated corticosteroid secretion. Effects on corticosteroid secretion were correlated with effects on cAMP accumulation and rates of cAMP production. Monolayers were incubated for 24 h in the absence or presence of each agonist alone or in combination with insulin. Insulin (1.7 x 10(-9) or 17.5 x 10(-9) M) caused about a 50% decrease in cortisol and androstenedione secretion in response to ACTH (10(-11) or 10(-8) M). Insulin also decreased ACTH-stimulated aldosterone secretion by cultured glomerulosa cells. Cpt-cAMP (10(-4) or 10(-3) M)-stimulated increases in cortisol and androstenedione secretion were inhibited by insulin, but to a lesser extent than those in response to ACTH. The inhibition of cpt-cAMP-stimulated steroid secretion was not related to increased degradation of the cyclic nucleotide. Increases in cortisol and androstenedione secretion caused by a submaximal concentration (10(-6) M) of forskolin were decreased 50-70% by insulin. In contrast, insulin failed to significantly affect cortisol or androstenedione secretion caused by a maximal concentration (10(-5) M) of forskolin. The secretory responses to Ang II (10(-8) M) were also unaffected by insulin. The effect of insulin to inhibit ACTH-stimulated steroid secretion was accompanied by a reduction in cAMP accumulation as well as an apparent inhibition of adenylate cyclase activation. These data indicate that the effect of insulin to attenuate ACTH-stimulated corticosteroid secretion results from both an inhibition of ACTH-stimulated adenylate cyclase activity and an antagonism of the intracellular actions of cAMP.

Regulation of leptin release by troglitazone in human adipose tissue.

In pieces of human subcutaneous adipose tissue incubated in primary culture for 48 hours, the release of leptin was stimulated by 50% in the presence of 3.3 micromol/L troglitazone. Insulin (0.1 nmol/L) and dexamethasone (200 nmol/L) stimulated leptin release by 30% and 300%, respectively. Troglitazone in combination with either insulin or dexamethasone had no effect on leptin release. Instead, troglitazone inhibited leptin release in the presence of both dexamethasone and insulin. The stimulatory effect of troglitazone on leptin release was also mimicked by 1 micromol/L 15-deoxy-delta(12-14)prostaglandin J2 (dPGJ2). However, if the concentration of dPGJ2 was increased to 10 micromol/L in the presence of dexamethasone, there was a decrease in leptin release, as well as of lactate formation and lipolysis. These data indicate that both stimulatory and inhibitory effects of troglitazone and dPGJ2 can be seen on leptin release by human adipose tissue.

Effects of norgestrel and metyrapone on pituitary-adrenal-ovarian function.

To assess the effects of d-norgestrel on pituitary-adrenal-ovarian function, basal levels and responses to metyrapone of urinary 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS), plasma cortisol (F), plasma delta4-androstenedione (A), plasma testosterone (T), plasma estrone (E1) and estradiol (E2), plasma and urinary LH and FSH were determined in 10 normal women before and while taking d-norgestrel 1 mg/day. Cortisol secretion rate (CSR) and binding capacities of cortisol binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) were also measured. Norgestrel did not significantly alter 17-KGS, 17-KS, F, LH, FSH, CSR, or the 17-KGS and 17-KS responses to metyrapone. Norgestrel reduced TeBG binding capacity but not CBG binding capacity. Norgestrel competitively inhibited the binding of dihydrotestosterone to TeBG under in vitro conditions. Levels of T, E2, and E1 were reduced by norgestrel. All measured hormone levels except FSH were increased following metyrapone prior to norgestrel administration. Norgestrel completely blocked the metyrapone-induced increases in LH and E2 and markedly reduced the E1 increase. Metyrapone reduced E2 during norgestrel treatment.

Efficacy of depot leuprolide in premenstrual syndrome: effect of symptom severity and type in a controlled trial.

OBJECTIVE: To determine whether depot leuprolide is effective in premenstrual syndrome (PMS) and whether symptom type or severity affects therapeutic or hormonal responses and the incidence of adverse events. METHODS: Twenty-five women who met strict diagnostic criteria for PMS completed a double-blind, placebo-controlled, 6-month crossover trial at a university medical center. Depot leuprolide (3.75 mg/month) or saline was administered intramuscularly for three consecutive treatment cycles. Efficacy, adverse events, and hormone concentrations were assessed at each visit. Repeated-measures analysis of variance was used to analyze continuous data, and ordinal and binary data were analyzed using nonparametric techniques. RESULTS: Depot leuprolide treatment was significantly more effective than placebo on all rating scales. Irritability, neurologic symptoms, breast tenderness, and fatigue were most responsive to treatment. Symptoms were reduced to follicular phase levels only in women without premenstrual depression. Those with moderate premenstrual depression improved but remained clinically symptomatic, whereas the group with severe premenstrual depression showed no improvement on any efficacy measure. Adverse events were lowest in those without premenstrual depression and highest in those with severe depression. Leuprolide suppressed estradiol and progesterone in most premenstrual depression groups but had varying effects on gonadotropins. CONCLUSIONS: Leuprolide treatment reduced both behavioral and physical symptoms and was well tolerated in the absence of severe premenstrual depression. Women should be evaluated for depression severity before receiving a GnRH agonist. The differential response to leuprolide suggests that it may possess diagnostic value in determining distinct subtypes of PMS.

Clinical findings and hormonal responses in patients with polycystic ovarian disease with normal versus elevated LH levels.

The clinical features, ovarian pathology, and hormonal responses to dexamethasone (Dex), Dex + ethinyl estradiol (EE), and Dex + hCG were compared in 5 women with polycystic ovarian disease (PCOD) who have normal 24-hr urinary luteinizing hormone (LH levels to 5 who had elevated urinary LH levels. No differences were noted in the clinical features. There was no correlation between ovary size and LH levels. Three in the normal-LH group had hyperthecosis. Plasma androstenedione (A) was more frequently elevated in the high-LH group. Dex + EE markedly increased LH secretion in the high-LH group, suggesting increased responsiveness of the positive feedback control mechanism of LH secretion in the high-LH group. There was a greater response of A, testosterone (T), and 17-ketosteroids to Dex + hCG in the normal-LH group. Those with high-LH levels did not exhibit a significant increase in A, T, and 17-KS with hCG. The limitations and usefulness of the Dex + hCG test are discussed. The hypothesis is advanced that the increased LH secretion in the high-LH group is due at least in part to positive feedback resulting from the increased A levels. The amount of 17beta-oxidoreductase activity in the ovary may influence LH secretion in PCOD.

Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year study.

OBJECTIVE: To evaluate prospectively maternal serum screening with alpha-fetoprotein (AFP), hCG, and unconjugated estriol (uE3) as a screen for fetal Down syndrome. METHODS: Women less than 35 years of age were offered screening between 15-20 weeks' gestation. Screening results calculated by an algorithm to be equal to or greater than 1:274 (the risk of a 35-year-old for fetal Down syndrome at the second trimester) were considered positive. If gestational age was confirmed by ultrasonography, genetic counseling and amniocentesis were offered. RESULTS: In the first 2 years of our program, 9530 women were screened, of which 686 (7.2%) were found to be screen-positive. Ultrasonographic examination explained the abnormal values in 379 (4.0%). The remaining 307 (3.2%) received genetic counseling and 214 (2.2%) elected amniocentesis or CVS. Four cases of fetal Down syndrome and one de novo chromosomal marker were detected. In three additional cases of fetal Down syndrome, triple-analyte screening failed to identify the pregnancies to be at increased risk. None of the seven cases of fetal Down syndrome would have been detected through screening with maternal serum alpha-fetoprotein (MSAFP) and age alone. CONCLUSIONS: Measurement of MSAFP, hCG, and uE3 in women less than 35 years old is an effective screening test for fetal Down syndrome, with a sensitivity of 57% in our study and an amniocentesis rate (false-positive rate) of 3.2%.

A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy.

OBJECTIVE: To compare the bioavailability of oral and intramuscular (i.m.) dexamethasone in third-trimester pregnant women. METHODS: Oral and i.m. dexamethasone levels were compared in a randomized, parallel, crossover bioavailability study involving 11 gravid women in the third trimester of pregnancy. Subjects were randomized to receive either 6 mg of i.m. or 8 mg of oral dexamethasone. The following week, the alternative regimen was administered. Serial blood samples were obtained after drug administration. Dexamethasone concentrations were measured by radioimmunoassay. Total area under the curve was compared for the oral and i.m. groups using a paired t test. RESULTS: Eight of the 11 women completed the study through 12 hours; all 11 women completed the study through 6 hours. Among the 11 women, peak levels of dexamethasone occurred 30 minutes after i.m. injection (mean +/- standard deviation, 101.7 +/- 19.2 ng/mL) and 120 minutes after oral administration (65.9 +/- 20.5 ng/mL). Area under the curve did not differ significantly between those receiving i.m. dexamethasone (258.3 +/- 50.0 ng/minute/mL) and those receiving oral dexamethasone (251.8 +/- 59.7 ng/minute/mL) when measured 6 hours after administration of the drug. Terminal half-lives were similar in the i.m. and oral groups. Similar findings were noted among the eight women who were studied through 12 hours. This study had a power of 87% to detect a 20% difference in area under the curve between the two groups. CONCLUSION: The bioavailability of 8 mg of oral dexamethasone is similar to that of a 6-mg IM dose, as determined by the area under the curve.

Features of Turner's syndrome in women with polycystic ovaries.

Four women with phenotypic features of Turner's syndrome and with poly cystic ovaries (PCO) are describe. In addition to the phenotypic features, Case 1 had primary amenorrhea and small PCO, Case 2 had a 46, XX/45, X karyotype (lumphocytes), Case 3 had enlarged PCO which contained a decreased number of oocytes, and Case 4 had enlarged PCO and was short in statute. These cases support the concept of a relation between PCO and the X chromosome. Some PCO may represent an intermediate condition in a spectrum that extends from the streak gonad of Turners syndrome to the normal ovary. Evidience for X chromosome involvement in PCO is summarized. The concept is advanced that at least some cases of OCO may be due to X chromosomal factors causing an abnormal follicular appartus.

Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women.

OBJECTIVE: To demonstrate bioavailability of 3 weeks of oral micronized DHEA and to delineate changes induced on insulin sensitivity, morphometric indexes, and lipoprotein profiles. DESIGN: Oral micronized DHEa (50 mg/d) was administered in 3-week treatments to 11 postmenopausal women in a prospective, placebo-controlled, randomized, blinded, crossover trial with an interarm washout. After dose (23 hour) serum DHEA, DHEAS, T, and cortisol levels were measured, as were fasting lipoproteins, oral glucose tolerance tests (OGTT), T-lymphocyte insulin binding and degradation, and urine collagen cross-links. Morphometric changes were determined by hydrostatic weighing. RESULTS: Dehydroepiandrosterone sulfate, DHEA, T, and free T increased up to two times premenopausal levels with treatment. Fasting triglycerides declined; no change in collagen cross-links or morphometric indexes was noted. Oral glucose tolerance test parameters did not change, but both T-lymphocyte insulin binding and degradation increased with DHEA. CONCLUSION: Fifty milligrams per day of oral DHEA gives suprahysiologic androgen levels; 25 mg/d may be more appropriate. Dehydroepiandrosterone enhanced tissue insulin sensitivity and lowered serum triglycerides. Rationale is provided for postmenopausal replacement therapy with this androgen.

Polycystic ovarian disease, maturation arrest of spermiogenesis, and Klinefelter's syndrome in siblings of a family with familial hirsutism.

A family with hirsutism in five generations in which polycystic or bilaterally enlarged ovaries were documented in three different sibships of two generations is described. Two brothers of one of the women with polycystic ovaries had a low or low-normal plasma follicle-stimulating hormone level and one of these had oligospermia due to maturation arrest of spermiogenesis. A third brother had Klinefelter's syndrome. Other abnormal features in the family included precocious adrenarche, beardless males, eunuchoidism, and prepubertal grand mal seizures.

Identification of fatty acid amides in human plasma.

A family of five long-chain fatty acid carboxamides has been identified and semi-quantified in human plasma by GC-MS. One saturated and four unsaturated amides were found. Luteal phase plasma from 16 women was studied, and all five of the amides were found in ten of the subjects, but none in the other six. The structure of these endogenous amides was established by comparing their GC and MS characteristics with those of the synthetic amides prepared by ammonolysis of corresponding long-chain fatty acid acyl chlorides.

Ligand-induced change in sedimentation behavior of human progestin receptors.

We determined the effect of ligand binding on the sedimentation behavior of cytosolic progestin receptors in human uterine leiomyomata, normal endometria and myometria. When cytosols were prelabeled with the tritiated progestin R5020, 4.4S and 7-8S receptors were demonstrated in all three uterine tissues; with postlabeling of fractionated gradients, 4.4S and 9-10S receptors were present. Sodium molybdate (20 mM) blocked the ligand-induced conversion of 9-10S to 7-8S receptors. The relative amount of 7-8S receptor increased with increasing amounts of ligand and time of incubation with ligand (up to 5 hrs); the amount of 9-10S receptor decreased with time. These data indicate that ligand binding to human uterine progestin receptors induces a change from a 9-10S to 7-8S form of receptor. Since molybdate blocks transformation of receptors and the ligand effect on receptor sedimentation, ligand binding to 9-10S receptor and the consequent conversion to 7-8S receptor may be a step preceding transformation of progestin receptors.