Synthesis of (4- 14 C)-labeled and non-labeled 3 , 15 -dihydroxy-5-pregnen-20-one and 3 , 15 -dihydroxy-5-androsten-17-one.
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17-alpha-Hydroxypregnenolone↗
Biomedical subjects
F Z Stanczyk
Publications and source records attributed to F Z Stanczyk.
Steroid production by early pregnancy human placental villi in culture.
Organ cultures prepared from human placentae obtained at 7-12 weeks of gestation were maintained for 3-13 days in Dulbecco's modified Eagle medium (DMEM). The addition of pregnenolone to the medium resulted in a dose-related increase in progesterone production and the addition of androstenedione resulted in a dose related increase in oestrogen production. More oestrone than oestradiol was measured in medium collected at the end of the first day of culture, but, on all subsequent days, oestradiol was the predominant oestrogen produced when androstenedione was added to the culture medium. When villi were incubated with [3H]androstenedione immediately after dissection most of the radiolabelled oestrogen recovered from the tissue and medium was oestrone; however, more [3H]oestradiol was recovered when villi were tested after 3 days of culture in DMEM. The addition of oestrone to the culture medium resulted in a dose related increase in oestradiol production with oestradiol accounting for a larger proportion of the total oestrogen in the day 2 and 3 medium samples than in the day 1 samples. These data demonstrate that the enzymes required for biosynthesis of progesterone and oestrogen from exogenous substrate are maintained for at least 13 days when early pregnancy placental villi are cultured in serum-free DMEM. However, a temporal change in the pattern of oestrogen synthesis does occur in culture, such that oestradiol rather than oestrone becomes the major product of androstenedione metabolism.
Androstenedione↗
Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women.
OBJECTIVE: To compare serum estrone sulfate (E1S) levels in postmenopausal women during long-term treatment with commonly prescribed doses of oral and transdermal estradiol (E2). DESIGN: A retrospective study performed in a University setting in the United States involving 33 healthy postmenopausal women. Two groups of postmenopausal women were studied: group 1 (n = 10) received 1 mg oral micronized E2 daily for 16 months; blood was drawn at 0, 7, and 15 months. Group 2 (n = 23) was randomized into three subgroups. Two of the subgroups (n = 8; n = 7) received E2 delivered at a rate of 0.05 mg/day and 0.1 mg/day, respectively, by transdermal patch, changed twice weekly; the third subgroup received a placebo (without E2) patch for 9 continuous months. Blood samples were drawn at 0, 6, and 9 months. Serum E1S and E2 were quantified by specific radioimmunoassays. Statistical analysis was performed by analysis of variance. RESULTS: After oral E2 treatment, E1S levels increased significantly (p < 0.01) from baseline, reaching an average level of 38.8 ng/mL at 15 months. After transdermal E2 treatment, E1S levels increased significantly, yet to a much lesser extent, reaching levels of 1.8 ng/mL and 3.2 ng/mL after 9 months of treatment with the 0.05 mg/day and 0.1 mg/day patches, respectively. CONCLUSIONS: Markedly elevated levels of E1S were found after long-term oral estrogen treatment. In comparison to the increase in E1S levels after long-term oral estrogen treatment, there was only a small increase in E1S levels after transdermal E2 therapy. This difference may be attributed to the higher dosage of oral E2 that is required because of the low bioavailability compared with the transdermal dosages.
Administration, Cutaneous↗
The effect of progestins on behavioral stress responses in postmenopausal women.
OBJECTIVE: We assessed the effects of progestin when added to estrogen on the adaptive patterns to provoked stress in postmenopausal women. METHODS: Fourteen postmenopausal women were randomized to receive either a transdermal estrogen patch (TE2) (n = 7) for 6 weeks or TE2 with added medroxyprogesterone acetate (10 mg) (TE2/MPA) (n = 7) for the last 10 days of the 6-week regimen. Behavioral stress tests were administered to each group, with measurements of biophysical and neuroendocrine responses. In a crossover fashion, after each group received the first treatment and testing, treatment was continued for another 6 weeks with the alternate regimen, at which time another stress test was administered. Responses to stress in the two treatment groups were compared to each other and to established placebo responses. RESULTS: Biophysical responses in the TE2 group were significantly blunted compared to both TE2/MPA and placebo responses (P < .05). Without MPA treatment, there were significantly blunted speech (P < .05) and cold pressor (P < .01) blood pressure responses. With added progestin, there was a greater systolic blood pressure response (P < .01) compared with estrogen alone. Both groups (TE2 and TE2/MPA) had blunted and nonsignificant responses of ACTH and cortisol upon testing, whereas the placebo group showed a significant response (P < .01). Plasma norepinephrine responses, however, were significantly blunted after TE2, compared with the increased responses observed with both TE2/MPA and placebo (P < .01). CONCLUSION: Although estrogen significantly reduces behaviorally induced stress reactivity in postmenopausal women, certain doses of progestin administration may blunt this effect.
Adaptation, Psychological↗
Comparison of estimates of insulin sensitivity in pre- and postmenopausal women using the insulin tolerance test and the frequently sampled intravenous glucose tolerance test.
OBJECTIVE: We assessed insulin sensitivity in women comparing the insulin tolerance test (ITT) with the intravenous glucose tolerance test with frequent sampling and computer modeling (FSIVGTT) and evaluated the effects of hormonal therapy in postmenopausal women using both methods. METHODS: This prospective study tested 18 premenopausal women and ten postmenopausal women randomized to receive either estrogen alone or estrogen with a sequential progestin for 6 months at a menopause research clinic. All subjects received an ITT and an FSIVGTT within 48-72 hours of each other in random sequence. Postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen for 6 months or 0.625 mg conjugated equine estrogen with medroxyprogesterone acetate, 10 mg, for 10 days each month for 6 months. Both the ITT and the FSIVGTT were repeated following hormonal therapy at 2 and 6 months. Plasma insulin and glucose were measured; insulin sensitivity was calculated after the ITT (Kitt) and the FSIVGTT (Si) at each visit in each group. RESULTS: A close correlation was found between Kitt and Si values at initial testing in both pre- and postmenopausal women and following both types of hormonal therapy (r = 0.76 for all tests, P < .001). A reduction in insulin sensitivity was observed in postmenopausal compared to premenopausal women; this occurred in five of ten postmenopausal women using the Kitt measurement and in four of ten women using Si. Estrogen replacement had a beneficial effect on insulin sensitivity. While Kitt increased by 24.2 +/- 9.6% (P < .05), the increase in Si (6.7 +/- 18%) was not significant because of the variability with this measurement. An attenuation in insulin sensitivity was seen with added progestin. Kitt values decreased by 17.7 +/- 7.7% and Si values by 31.9 +/- 12%. Similar findings were noted at 2 and 6 months. CONCLUSIONS: The ITT and FSIVGTT provide quantitatively similar information regarding insulin sensitivity in healthy women. A mild degree of insulin resistance appears to be present in some healthy postmenopausal women. Estrogen appears to improve insulin sensitivity, while added progestin may attenuate this beneficial effect.
Adult↗
Plasma prostaglandin E(2) metabolite levels during labor induction with a sustained-release prostaglandin E(2) vaginal insert.
OBJECTIVE: To measure prostaglandin E(2) levels during labor induction with a sustained-release vaginal polymer insert (prostaglandin E(2) insert) and to determine whether Bishop score change correlated with tachysystole. METHODS: Twelve primiparas and 12 multiparas were treated with a 0.3 mg per hour sustained-release polymer vaginal prostaglandin E(2) insert for up to 24 hours. Bishop score was assessed at start and end of therapy, and serum samples were collected at 4-hour intervals. Prostaglandin E(2) metabolite (PGEM) levels were measured by specific enzyme immunoassay. RESULTS: Exposure averaged 13.5 +/- 7.2 hours. Four patients (16.7%, three nulliparas) had tachysystole. Mean PGEM levels increased from 187 +/- 42 pg/mL at baseline to 548 +/- 110 pg/mL at 12 hours (P <.05) and remained relatively stable thereafter. Nulliparas with Bishop score changes of four points or more had the highest increase, with average peak levels of 985 +/- 109 pg/mL, compared with 452 +/- 58 pg/mL for all others (P <.001). Patients with tachysystole had higher 4-hour (P <.01) and overall (P <.04) increases in PGEM level. Removal of the insert led to an average decrease of 335 pg/mL in PGEM levels (P <.01). The decrease correlated with the PGEM level measured before removal (r =.94, P <.0001) and the maximum PGEM increase from baseline (r =.94, P <.0001). The mean mixed venous cord PGEM level was 409 +/- 375 pg/mL. CONCLUSION: Administration of the prostaglandin E(2) insert led to a sustained increase in circulating PGEM levels in women who had labor induction. Peak PGEM levels correlated with Bishop score improvement. Rapid increases in prostaglandin E(2) levels might cause tachysystole.
Administration, Intravaginal↗
Altered regulation of insulin-like growth factor binding protein-1 in patients with polycystic ovary syndrome.
OBJECTIVE: Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women. METHODS: We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 +/- 1 and 22 +/- 1 years, respectively). All subjects were studied after an overnight fast between days 5-8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of a euglycemic clamp, and, in a subsequent cycle, the administration of a long-acting somatostatin analogue (octreotide, 100 micrograms) given subcutaneously. Blood samples were collected before treatment, every 15 minutes for 6 hours after insulin, and every 30 minutes for 3 hours after octreotide administration. Serum levels of IGF-I, IGFBP-1, IGFBP-3, and insulin were measured by specific immunoassays. RESULTS: Compared with the controls, patients with PCOS had significantly higher insulin levels, similar IGF-I and IGFBP-3 levels, and significantly lower IGFBP-1. Insulin did not change serum IGF-I levels in either group, although a significant decrease in IGFBP-1 levels occurred in normal women but not in patients with PCOS. Octreotide treatment also did not change serum IGF-I levels in either group, but serum insulin levels decreased significantly and IGFBP-1 levels increased significantly in both groups; this response was significantly greater in controls. CONCLUSIONS: Our data are compatible with the notion that regulation of IGFBP-1 is altered in women with PCOS and that several factors may be involved.
Adult↗