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Biomedical subjects

U Goebelsmann

Publications and source records attributed to U Goebelsmann.

At least 55 records · Page 3Linked to original sources
PubMed1980

Radioimmunoassay of plasma ethinylestradiol in the presence of circulating norethindrone.

A reliable radioimmunoassay (RIA) for the measurement of ethinylestradiol (EE2) in plasma after the separation of norethindrone (NET) by column chromatography has been developed. The procedure involves diethyl ether extraction, followed by celite column partition chromatography to separate NET from EE2. An antiserum against ethinylestradiol-7-(3-thiopropionic acid)-bovine serum albumin conjugate was employed. Tritiated EE2 was used as the radioligand. The separation of bound from free 3H-EE2 was carried out with dextran-coated charcoal. This RIA procedure was used to measure plasma EE2 at specified time intervals in three women following oral administration of a tablet containing EE2 (0.12 mg) and NET (1.0 mg). The results show that EE2 is rapidly absorbed after oral administration. Peak concentrations of plasma EE2 were reached within 1.0 to 1.5 hours and then declined biphasically. The EE2 alpha phase half-life values in three subjects were 1.5, 2.8 and 3.8 hours. By comparison, the half-life values for the beta phase for the same three women were 6.2, 12.3 and 14.5 hours, respectively. Plasma samples were also analyzed for NET by RIA. The half-life values for the beta phase for EE2 and NET in the three subjects were similar.

Administration, Oral↗
PubMed1980

Serum levels of ethinylestradiol following its ingestion alone or in oral contraceptive formulations.

The pharmacodynamics of ethinylestradiol (EE2) were studied utilizing a specific radioimmunoassay to measure serum levels in subjects ingesting EE2 alone or in combination with various gestagens. Following the administration of a single oral dose of 20 micrograms of EE2 to three postmenopausal women, peak serum levels ranging from 29 to 58 pg/ml were reached within one hour. Levels fell below the sensitivity of the assay (20 pg/ml) 2, 5 and 8 hours after ingestion. In normal menstruating women, peak serum EE2 concentrations averaged 84 +/- 27 pg/ml after the ingestion of 35 micrograms EE2 and 0.5 mg norethindrone, 152 +/- 57 pg/ml after the ingestion of 50 micrograms mestranol and 1.0 norethindrone and 201 +/- 11 pg/ml after the ingestion of 50 micrograms EE2 and 0.5 mg norgestrel. After the ingestion of mestranol, peak serum levels of EE2 were less than and occurred later than peak levels obtained after the ingestion of the same dose of EE2.

Adult↗
PubMed1979

Steroid localization in granulosa-theca tumors of the ovary.

Eleven granulosa-theca tumors (seven pure granulosa and four with associated theca elements) were examined for the presence of estradiol, progesterone and testosterone using an indirect immunoperoxidase technique on formalin-fixed paraffin embedded tissue. In ten patients the endometrium was studied histologically and significant endometrial hyperplasia consistent with estrogen production by the tumors was found. Estradiol was localized in granulosa cells (nonluteinized) in all 11 cases and in luteinized theca cells in three of the four cases in which theca elements are present. In contrast, progesterone was always detected in luteinized theca cells and in granulosa cells in over one half the cases. Testosterone was also present in granulosa cells in just over half the cases but tended to be only weakly positive. The nonluteinized stromal cells were negative for all steroids. These results are compatible with the concept that in granulosa-theca tumors, both granulosa and theca cells can produce a wide range of steroid hormones but that the predominant steroid present in granulosa cells is estradiol, while progesterone is the predominant steroid in luteinized theca cells.

Adult↗
PubMed1979

Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome.

A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.

Adrenocorticotropic Hormone↗
PubMed1979

Roles of estradiol and progesterone in eiliciting the midcycle luteinizing hormone and follicle-stimulating hormone surges.

The positive feedback effects of estradiol (E2) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterupted E2 replacement by subdermal implants. Basal serum E2 levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E2B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E2B injections. In all three subjects, increasing serum E2 levels mimicking the preovulatory E2 peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E2 concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E2 concentrations had risen or when P levels increased without a rise in serum E2, neither a serum LH nor FSH peak was observed. When administered concomitantly, E2B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E2 is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak.

Adult↗
PubMed1978

An immunohistological study of steroid localization in Sertoli-Leydig tumors of the ovary and testis.

Nine ovarian Sertoli-Leydig tumors, showing varying degrees of differentiation, one pure ovarian Sertoli cell tumor, and one poorly differentiated stromal tumor of the testis, were examined for the presence of testosterone, estradiol and progesterone with an indirect immunoperoxidase method on formalin fixed paraffin embedded tissue. Clinically all nine patients with Sertoli-Leydig tumors had evidence of increased androgen production, manifested by either hirsutism or virilization; elevated serum testosterone was found in all four patients in whom it was measured. The patients with the pure ovarian Sertoli cell and testicular tumors were asymptomatic except for the presence of a mass. Testosterone was identified in Leydig cells in nine instances, in Sertoli cells in six, and in poorly differentiated spindle cells resembling the mesenchyme of the embryonic gonad in two. Cells with vacuolated cytoplasm, both Sertoli and Leydig cells, though positive for lipid were consistently negative for testosterone. Estradiol was present in Leydig cells in nine instances, in Sertoli cells in five, and in primitive gonadal stomal cells in two. The pattern of distribution was similar to that of testosterone but the intensity of the reaction for estradiol was generally less than that for testosterone. Progesterone was identified in Sertoli cells in one instance and was weakly positive in Leydig cells in three instances. The presence of testosterone and estradiol in both Sertoli and Leydig cells as well as in primitive spindle cells resembling those found in the embryonic gonad suggests that the latter cell is the precursor for both Sertoli and Leydig cells.

Adolescent↗
PubMed1978

A radioimmunoassay for norethindrone (NET): measurement of serum NET concentrations following ingestion of NET-containing oral contraceptive steroids.

A sensitive and reliable radioimmunoassay (RIA) for the measurement of norethindrone (NET) in serum has been established employing anti-11 alpha-hydroxynorethindrone 11-hemisuccinyl-bovine serum albumin serum in conjunction with norethindrone-3-(0-carboxymethyl) oximino-[125I]-iodohistamine. Of a number of ring A reduced NET metabolites, only 17 beta-hydroxy-17 alpha-ethinyl-5 beta-estran-3-one (43%) and 17 alpha-ethinyl-5 alpha-estrane-3 beta, 17 beta-diol (15.7%) cross-reacted appreciably in this RIA. Ethinyl estradiol (EE2) and mestranol (MEE2) exhibited cross-reactions of only 1.1 and 0.4%, respectively. Serum NET levels were measured in four groups of 3 women, each ingesting either 1 mg NET plus 0.05 mg MEE2 (Norinyl 1 + 50 or Ortho Novum 1/50), 0.5 mg NET plus 0.035 mg EE2 (Brevicon) or only 0.35 mg NET (Micronor) daily for 5 consecutive days. Peak serum NET levels were observed within 1/2 to 4 hours after oral intake and fell precipitously thereafter. After reaching a maximum, serum NET concentrations declined in a manner consistent with at least two disposition phases. The average half-life for the first disposition phase was 2.3, 3.4, 3.9 and 4.4 hours in subjects ingesting Norinyl 1 + 50, Ortho Novum 1/50, Brevicon and Micronor, respectively. Peak and 3-hour post-ingestion serum NET concentrations were dose-related but showed considerable subject-to-subject variations. Following discontinuation of tablet intake, serum NET levels remained detectable (greater than 0.05 ng/ml) for at least 5 days in all 3 women who had taken Ortho Novum 1/50, but in none of the other 9 volunteers. These results suggest that different preparations of identical doses and combinations of oral contraceptive steroids may yield different serum NET profiles. However, due to considerable subject-to-subject variations, larger numbers of subjects are required for a conclusive investigation.

Adult↗
PubMed1978

A double-antibody radioimmunoassay for serum progesterone using progesterone-3-(O-carboxymethyl) oximino-[125I]-iodo-histamine as radioligand.

A reliable, convenient and economical radioimmunoassay (RIA) for serum progesterone has been established and tested. This procedure employs diethyl ether extraction followed by RIA utilizing rabbit anti-11 alpha-hydroxyprogesterone 11-hemisuccinyl-bovine serum albumin (progesterone-11 alpha-BSA) serum, progresterone-3-(O-carboxymethyl) oximino-[125I]-iodohistamine (progesterone-3-[125I]) as radioligand and goat anti-rabbit gamma globulin as second antibody. In conjunction with antiprogesterone-11 alpha-BSA serum, the overall assay specificity of the progesterone-3-[125I] RIA is similar to that of the [3H]-progesterone method using dextran-coated charcoal. The results of serum progesterone measurements during the menstrual cycle obtained by the progesterone-3-[125I] RIA appear comparable to those of [3H]-progesterone assays which employ similar anti-progesterone-11 alpha-BSA sera. The progesterone-3-[125I] double-antibody RIA, however, is more convenient and less expensive than the [3H]-progesterone RIA method.

Antibodies, Anti-Idiotypic↗
PubMed1978

Clinical, endocrinological, and enzymatic characterization of two patients with 5 alpha-reductase deficiency: evidence that a single enzyme is responsible for the 5 alpha-reduction of cortisol and testosterone.

Two siblings with 46,XY male pseudohermapthroditism were demonstrated to have the phenotype characteristic of 5 alpha-reductase deficiency, namely normal testes and male Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle) terminating in a blind-ending vagina. Clitoromegaly was present at birth and increased further at the time of expected puberty. The diagnosis of 5 alpha-reductase deficiency was confirmed by demonstration of male levels of testosterone and testosterone precursors before and after hCG administration, elevated plasma testosterone to dihydrotestosterone and urinary etiocholanolone to androsterone ratios, and by in vitro studies indicating 5 alpha-reductase enzyme deficiency in the epididymis of one patient. Studies of control and mutant epididymal microsomes indicated that a single enzyme is responsible in the normal person for the 5 alpha-reduction of testosterone and cortisol (and probably other delta 4-3-ketosteroids as well) and that 5 alpha-reductase activity is undetectable for all substrates examined in the mutant. This finding explains why the formation of 5 alpha-reduced glucocorticoids is also defective in the disorder.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1978

Evaluation of the contraction stress test before 33 weeks' gestation.

The value of the contraction stress test (CST), although well documented in late pregnancy, has been questioned earlier in gestation. We have evaluated the reliability of the CST in 102 patients tested before 33 weeks' gestation. Eighteen patients with a positive CST had a significantly higher incidence of abnormal urinary estriol excretion (60% of patients), low Apgar scores (44%), growth retardation (39%), and perinatal mortality (277/1000) than did 84 women without a positive CST. Two stillbirths and 3 neonatal deaths occurred in the positive CST group. None of the neonatal losses was due to unnecessary premature intervention. Four patients with a positive CST showed no signs of fetal compromise, a false positive rate of 22%. Delivery was safely delayed an average of 6.1 weeks in patients without a positive CST. These findings demonstrate the predictive value of the CST and support its clinical application early in the third trimester.

Apgar Score↗