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Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 145 records · Page 8Linked 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

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↗
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

Isolation fo 15alpha-hydroxypregnenolone and 15alpha-hydroxydehydroisoandrosterone from human pregnancy urine.

15alpha-Hydroxydehydroisoandrosterone and 15alpha-hydroxypregnenolone were isolated from hydrolyzed extracts of human late pregnancy urine and identified by means of the isotope dilution technique. In two separate determinations the excretion rate of 15alpha-hydroxydehydroisoandrosterone was found to be 1.7 and 3.2 microgram per day while that of 15alpha-hydroxypregnenolone was 1.7 and 2.9 microgram per day. It is postulated that 15alpha-hydroxydehydroisoandrosterone might serve as a precursor of 15alpha-hydroxylated estrogens already isolated from late pregnancy urine. Similarly, 15alpha-hydroxypregnenolone might be an endogenous precursor of 15alpha-hydroxyprogesterone.

17-alpha-Hydroxypregnenolone↗
PubMed1978

Formation of 15alpha-hydroxyestriol and 15alpha-hydroxyestradiol from C19 15alpha-hydroxylated precursors in human pregnancy.

A mixture of 3H-15alpha-hydroxyandrostenedione and 14C-15alpha-hydroxydehydroisoandrosterone was injected intravenously into two subjects in the third trimester of pregnancy and, in a second study, directly into two fetuses in utero during transfusion for erythroblastosis fetalis. The urine was collected for 4-5 days and steroid conjugates in the urine were hydrolyzed into sulfate and glucosiduronate fractions. From the glucosiduronate fraction 15alpha-hydroxyestriol, 15alpha-hydroxyestradiol, 15alpha-hydroxyandrostenedione and 15alpha-hydroxydehydroisoandrosterone were isolated. No metabolites were identified in the sulfate fraction of the urine. A marked difference was observed in the metabolism of 15alpha-hydroxyandrostenedione and 15alpha-hydroxydehydroisoandrosterone which is dependent on the route of administration of the substrates. Both substrates were converted to 15alpha-hydroxyestriol and 15alpha-hydroxyestradiol, and the 3H/14C ratios and percentage conversions suggest that 15alpha-hydroxyandrostenedione seems to be a better precursor of the urinary 15alpha-hydroxylated estrogens than 15alpha-hydroxydehydroisoandrosterone. The 3H/14C ratios also suggest that 15alpha-hydroxydehydroisoandrosterone was converted to 15alpha-hydroxyestriol via 15alpha-hydroxyandrostenedione, and that the formation of 15alpha-hydroxyestradiol from 15alpha-hydroxydehydroisoandrosterone via 15alpha-hydroxyandrostenedione is a pathway of minor importance. Finally, 15alpha-hydroxydehydroisoandrosterone was recovered from the urine only when the precursors were injected into the maternal circulation. Also, an unknown metabolite containing only 14C was detected in the glucosiduronate fraction of the urine of each subject.

Androstenedione↗
PubMed1977

Serum levels of d-norgestrel, luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone in women during and following ingestion of combination oral contraceptives containing dl-norgestrel.

Three formulations of dl-norgestrel were administered daily to groups of three women for five consecutive days. The serum levels of d-norgestrel were related to the dosage of dl-norgestrel ingested. Peak concentrations in the circulation of synthetic gestagen were attained a half hour to three hours after oral administration, followed by a rapid and sharp decline in levels until the next dose. Three women received 500 micrograms of dl-norgestrel and 50 micrograms of ethinyl estradiol for 21 days followed by six to seven days of no medication for two consecutive cycles. The gonadotropins remained suppressed for four to six days when therapy was discontinued. The daily concentrations of estradiol varied from less than 5 to 81 pg. per milliliter, and there was no difference in estrogen values during the nontreatment and treatment days. Due to the long half life of norgestrel, the one-week pill-free interval is not long enough for the complete recovery of the reproductive axis from the inhibition of oral contraceptives.

Adult↗
PubMed1977

Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA.

A sensitive radioimmunoassay measuring serum medroxyprogesterone acetate (MPA) has been developed in order to measure and correlate serum MPA concentrations and ovarian function in women following im administration of deop-MPA (DMPA), employing goat anti-MPA-3-(O-carboxymethyl) oxime-bovine serum albumin and MPA-3-(O-carboxymethyl) imino-125I-iodohistamine. In the 3 women studied, im injection of 150 mg of DMPA yielded brief initial serum MPA concentrations ranging from 1.5 to 3 ng/ml for a few days. Serum MPA concentrations gradually declined and remained relatively constant at about 1 ng/ml for 2 to 3 months, declined gradually thereafter reaching 0.2 ng/ml during the 6th month and became undetectable (less than 0.02 ng/ml) about 7-1/2 to 9 months following administration. Serum estradiol remained at early to midfollicular phase levels for 4 to 6 months after DMPA injection and rose to preovulatory levels when serum MPA levels fell below 0.5 to 0.25 ng/ml. Ovulation, however, as evidenced by serum progesterone concentrations did not occur, apparently due to suppression of the LH peak by positive feedback inhibition. Prolonged inhibition of cyclic ovarian function following DMPA injection is caused by slow MPA absorption and persists until serum MPA levels have decreased below 0.1 ng/ml or become undetectable about 7 to 9 months after DMPA administration.

Adult↗
PubMed1975

Radioimmunoassay of serum medroxyprogesterone acetate (Provera) in women following oral and intravaginal administration.

A radioimmunoassay (RIA) method for measuring medroxyprogesterone acetate (MPA, Provera) in serum has been developed utilizing benzene:iso-octane extraction, 3H-MPA to assess procedural losses, goat anti-MPA-3-(0-carboxymethyl) oxime-bovine serum albumin serum and dextran-coated charcoal separation. Control serum blanks were undetectable, 200 pg/ml of MPA was measurable with a high reliability, and intra- and interassay coefficients of variation were 6 and 13 percent, respectively. MPA added to control serum was quantitatively recovered. Serum MPA levels measured in 2 women after ingestion of 10 mg MPA rose to 3.4 to 4.4 ng/ml within 1 to 4 hours after oral intake and fell rapidly thereafter to 0.3 to 0.6 ng/ml within 24 hours. Insertion of Silastic intra-vaginal rings (IVRs), containing 100 or 200 mg of MPA, into 4 women for periods of 3 weeks resulted in a rapid rise of serum MPA after insertion, rather stable MPA levels of 0.9 to 1.6 ng/ml while the IVRs were in place, and a rapid decline of serum MPA following IVR removal. Serum estradiol-17beta and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited. The serum MPA levels observed in this study were approximately 5 times lower than those reported by other investigators using a double-antibody RIA of MPA in unextracted serum.

Administration, Oral↗
PubMed1975

In vitro steroid metabolic studies in testicular 17 beta-reduction deficiency.

In order to document testicular 17beta-reduction deficiency (17RD) and to search for additional metabolic aberrations possibly associated with this disorder, the metabolism of 14C-labeled pregnenolone (delta5P), 17-HYDROXYPROGESTERONE (17OHP), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and estrone (E1) was studied in testicular minces from a 46-year-old male pseudohermaphrodite (MPH) with highly elevated testicular A and minimal T secretion but normal extragonadal conversion of A to T. Testicular minces from a 20-year-old MPH with apparently normal testicular T biosynthesis served as a control. The results of this investigation show that the 17RD testes metabolized delta5P along delta5- and delta4- pathways but, in contrast to the control, converted more 17OHP, metabolizing it predominantly to A rather than T, failed to reduce DHEA to androst-5-ene-3beta,17beta-diol, metabolized DHEA very efficiently to A and produced little T, and converted only minimal quantities of A and E1 to their 17beta-reduced counterparts. 17beta-Reduction increased slightly but was far from being restored to control levels upon addition of NADH plus NADPH. However, oxidation of T to A by 17RD testicular minces, with and without additional NAD plus NADP, was comparable to that by the control. These results document 17RD for A, DHEA and E1 and suggest that the lack of elevated 17OHP and DHEA secretion by the 17RD testes was due to increased 17, 20-lyase and perhaps elevated 3beta-hydroxysteroid dehydrogenase and/or isomerase activity. The observation that 17beta-reduction was only slightly increased upon addition of NADH plus NADPH, but that oxidation of T to A was normal, is consistent with the assumption that more than one 17beta-hydroxysteroid dehydrogenase may be involved in testicular 17beta-reduction and/or 17-oxidation, and that the 17RD testes studied either lacked the enzyme which acts predominantly as 17beta-reductase or that the affinity of this 17beta-reductase for reduced cofactor(s) and/or substrates was abnormal.

Adult↗