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Biomedical subjects

E Diczfalusy

Publications and source records attributed to E Diczfalusy.

At least 73 records · Page 4Linked to original sources

Hormonal consequences of missing the pill during the first two days of three consecutive artificial cycles.

The hormonal effects of the deliberate omission of a low-dose combined oral contraceptive pill (30 micrograms ethinyl estradiol + 150 micrograms levonorgestrel) during the first two days of three consecutive artificial cycles were studied in 10 women. The plasma levels of estradiol, progesterone, levonorgestrel and--whenever justified--of LH were measured three times weekly (Mondays, Wednesdays and Fridays) throughout a 90-day period, and the ovarian reaction to the prolongation of the pill-free period from 7 to 9 days was assessed. One subject (with a premature LH surge) showed a marked follicular and an inadequate luteal activity in 2 of 3 cycles. The remaining cycles were characterized by a varying degree of follicular activity associated with the absence of any luteal function. None of the subjects exhibited peripheral steroid levels indicating a normal ovulatory cycle. The results are interpreted as suggesting that repeated prolongation of the pill-free period from 7 to 9 days might result in a gradual increase in ovarian activity.

Adult↗

Return of ovulation following a single injection of depo-medroxyprogesterone acetate: a pharmacokinetic and pharmacodynamic study.

The effect of a single dose of 150 mg of depo-medroxyprogesterone acetate (DMPA) on pituitary, ovarian and endometrial function was assessed in relation to the peripheral levels of the compound in 8 women. The levels of medroxyprogesterone acetate (MPA), follitropin (FSH), lutropin (LH), prolactin, estradiol (E2) and progesterone ( Prog .) were measured 3 times a week during a pretreatment (control) cycle and then daily during postinjection weeks 14-17, 22-25 and 30-33. An endometrial biopsy specimen was obtained during postinjection weeks 17, 25 and 33. In three out of 8 subjects the daily hormone assays carried out during postinjection weeks 30-33 indicated anovulatory periods; in these subjects peripheral blood was drawn daily during postinjection weeks 46-49 and a fourth endometrial biopsy was taken during week 49.

Adult↗

The early history of estriol.

The early history of estriol is reviewed with special emphasis on its isolation, identification, quantitation in tissues and body fluids and its unique biogenesis in the human feto-placental unit. The relationship to epimeric estriols and acidic estrogens and the pharmacokinetic and pharmacodynamic properties which led to a widespread therapeutic use of this compound are also discussed.

Animals↗

Evidence for the prostatic origin of immunoreactive inhibin-like material in human seminal plasma.

Inhibin is defined as a gonadal peptide exerting an inhibitory effect on the secretion of follicle-stimulating hormone (FSH) by the pituitary. Using a radioimmunoassay (RIA) procedure developed for a homogeneous inhibin-like peptide with a molecular weight of 14 000 daltons isolated from human seminal plasma, immunoreactive inhibin-like matrial (ILM) was quantitated in serum, urine and semen of men in order to investigate its origin. Vasectomy did not result in a significant reduction in seminal plasma ILM. Determination of ILM immunoreactivity in ejaculates form normal men and semen samples characterized by prostate-rich and prostate-deficient secretions, indicated high levels of ILM in the prostatic secretions. Immunoreactive ILM levels estimated in different fractions of split ejaculates from normal men paralleled those of zinc and acid phosphatase activity and were significantly higher in fractions representing prostatic secretions compared to those representing the secretions of seminal vesicles. Estimation of ILM in semen, serum and urine from bilaterally gonadectomized men showed that immunoreactive ILM levels remained high after gonadectomy. It is concluded that the bulk of the immunoreactive ILM present in the semen, blood and urine of men is not secreted by the testes. The principal site of origin of this material, at least in semen, appears to be the prostate.

Acid Phosphatase↗

Heterologous radioimmunoassay of monkey luteinizing hormone: a critical assessment.

Available reagents for the immunoassay (RIA) of luteinizing hormone (LH) in monkeys, including a cynomolgus (cynLH) tracer, an antiserum against human chorionic gonadotropin (hCG), and a rhesus standard (rhLH), were assessed using an in vitro bioassay and the RIA in connection with fractionation by high-resolution isoelectrofocusing. The data presented indicate that the RIA system represents a significant improvement over the ovine-antiovine system. Since, however, the sensitivity of the RIA is some 50 times less than that of the in vitro bioassay, and since the rhLH standard is heavily contaminated with FSH, it is felt that until the advent of a homologous RIA, the in vitro bioassay is the method of choice.

Animals↗

Biological and immunological characterization of purified follicle-stimulating hormone preparations from monkey pituitaries.

The suitability of a purified rhesus (rhFSH) and cynomolgus (cynFSH) follicle-stimulating hormone (FSH) preparation to replace the expired LER 1909-2 reference standard in the immunoassay of monkey FSH was assessed using an in vitro bioassay and two heterologous radioimmunoassay (RIA) procedures in combination with fractionation by high-resolution isoelectrofocusing. The results presented indicate that rhFSH is unsuitable for the replacement of LER 1909-2 as a standard, though cynFSH might be suitable after the removal of its LH contamination.

Animals↗

Characterization of various molecular species of follicle-stimulating hormone in baboon pituitary preparations.

The properties of baboon (Papio hamadryas) follicle-stimulating hormone (bFSH) have been studied after isoelectrofocusing (IEF) of individual pituitary extracts from five female and three male baboons and of a partially purified bFSH preparation (CM-1). The in vitro bioactivities of the female and male pituitary extracts and of CM-1 were 6.0 (range 4.1-9.6), 10.8 (6.9-18.2), and 34.1 (30.3-38.3) mg equivalent of LER 1909-2 reference standard per mg protein, respectively. The corresponding ratios of bioactivity to immunoreactivity (B/I) were 1.72 (range 1.31-2.06), 1.82 (1.53-2.25), and 1.54 (1.51-1.58), respectively. There was a significant increase (p less than 0.05) in all B/I ratios after IEF, due to a diminished immunoreactivity without any loss in bioactivity. Several molecular forms of bFSH were observed with pI values ranging from 4.5 to 7.5, with maximum activity between pH 4.5 to 6.0. The IEF profiles of female and male pituitaries and of the purified bFSH preparation were similar. However, the B/I ratios of the different molecular species of bFSH increased with increasing pI values in every case. It is concluded that there is a significant heterogeneity of bFSH in crude as well as in purified pituitary extracts, but neither the sex of the animals nor the process of purification influenced the quantity and distribution of various molecular species.

Animals↗

Pituitary, ovarian and endometrial effects of progesterone released prematurely during the proliferative phase.

The pituitary, ovarian and endometrial effects of premature exposure to progesterone during the proliferative phase were investigated in 18 normally menstruating women. Daily blood samples were drawn during a control cycle and an endometrial biopsy was obtained on cycle day 6 (in 9 subjects) and on cycle day 11 (in 9 subjects), respectively. Daily blood samples were drawn again throughout a treatment cycle, in which a vaginal delivery system releasing progesterone at a constant rate of 1.4 mg/24 h was inserted and left in situ for 96 hours during cycle days 2-6 (9 subjects) and cycle days 7-11 (9 subjects), respectively. On the 6th and 11th cycle day, respectively, the devices were removed and another biopsy specimen was obtained. In all blood samples the levels of immunoreactive lutropin (LH), estradiol (E2), 17-hydroxyprogesterone (17-HO-P), progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-HO-P) were estimated by radioimmunoassay. Insertion of the devices resulted in a rapid, approximately six-fold increase (from 0.5 to 3.0 nmol/l) in P levels and an approximately three-fold (from 0.5-0.6 to 1.5-2.0 nmol/l) increase in 20 alpha-HO-P levels. A high degree of correlation was found between P and 20 alpha-HO-P levels. No major changes were observed in the profiles and levels of the other hormonal indices studied. However, premature exposure to small amounts of P during cycle days 2-6 resulted in a significant decrease in the ratio of the E2 to LH peaks and exposure during cycle days 7-11 gave rise to a significant increase in the ratio of the length of follicular to luteal phases. Progesterone released during the early proliferative phase (days 2-6) exerted little, if any, effect on the appearance of the endometrium. However, the same dose of P released during the late proliferative phase (days 7-11) significantly diminished the number of glandular mitoses, the height of the glandular epithelium, reduced pseudostratification and the number of plasmolemmal vesicles, but did not induce any subnuclear vacuolation, predecidual reaction or leucocytic infiltration. It is suggested that systematic studies involving the exposure to progestogens in normally menstruating women during cycle days 7 to 11 will provide a reliable and practical method for the comparative assessment of the potency profile of individual progestogens in women.

17-alpha-Hydroxyprogesterone↗

Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme.

The great demand for improved long-acting injectable steroid contraceptives, particularly in developing countries, and the relative lack of interest from the pharmaceutical industry to develop such products stimulated WHO to launch a synthetic and screening programme to find improved, safe and acceptable injectable preparations. More than 210 esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) have been prepared in university-based research laboratories situated mainly in developing countries, and then screened by NICHHD in animal models. The following three compounds, levonorgestrel butanoate, cyclopropylcarboxylate and cyclobutylcarboxylate, proved to be particularly long-acting when administered as microcrystalline suspensions. The overall strategy of this research and development programme is described.

Animals↗

Pharmacodynamic effects of ethinyl estradiol in women using vaginal devices releasing small doses of levonorgestrel at a constant rate.

Eight normally menstruating women were provided with vaginal devices releasing levonorgestrel (NOG)4) at a constant rate of 20 micrograms/24 h. On day 71 or 72 following the insertion of the device, oral doses of 50 micrograms of ethinyl estradiol (EE) were administered daily for one week. Peripheral blood samples were drawn three times weekly during a pretreatment (control) cycle and from day 29 of the treatment period. The levels of progesterone (P), estradiol (E2) and NOG were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by a steady state polyacrylamide gel electrophoresis and the percentage of binding of NOG, testosterone (T) and E2 by equilibrium dialysis of diluted plasma. An endometrial smear and a biopsy were taken from each subject on 3 occasions, viz. during the control cycle (cycle day 20-22), during the period with the NOG-releasing device in situ (44-50 days after the insertion of the device), and on the 7th day of concomitant EE administration.

Adult↗

Microheterogeneity of luteinizing hormone in pituitary glands from women of pre- and postmenopausal age.

Luteinizing hormone from the pituitaries of women of premenopausal (Pre-M) and postmenopausal (Post-M) age has been studied to further understand the variations in the quality of plasma LH in women of different ages. The median and range for bioactive LH was 101: 85-155 IU/mg protein and 83: 52-201 IU/mg protein for the Pre- and Post-M groups respectively. The ratios of LH bioactivity/immunoreactivity (B:I) were 1.04 +/- 0.13 (Pre-M) and 0.97 +/- 0.02 (Post-M). Broad range isoelectrophoretic profiles of the pituitary extracts revealed a heterogeneous population of coincident bioactive and immunoreactive LH peaks. Recoveries from the columns were similar in both groups and B:I values of the LH material throughout the columns were between 0.5 and 2.0 in over 90% of the fractions. Between 31.8 and 36.6% of the LH from both groups appeared between pH 7 and pH 8. The most striking difference between the two groups was that greater than 34% of the bioactive LH from the Post-M pituitaries, but less than 6% of the LH from the other group had migrated as a major discrete peak to an acidic region of pH less than 6. We conclude that although there is no difference in total LH activity in the pituitaries from the two groups, substantially more 'acidic' LH material is stored in the postmenopausal pituitaries. These observations are consistent with the recent finding of greater circulating levels of acidic LH in plasma from post-menopausal women.

Adult↗

Effect of vasectomy on the steroid profile of human seminal plasma.

The effect of vasectomy on the steroid profile of seminal plasma was studied in 19 healthy men at 4-monthly intervals during a 2-year post-vasectomy period. The steroids analyzed by radioimmunoassays were: androstenedione (A), testosterone (T), dihydrotestosterone (DHT), oestradiol (E2) and the sulphoconjugated forms of pregnenolone (delta 5P-S), dehydroepiandrosterone (DHEA-S), testosterone (T-S), dihydrotestosterone (DHT-S), oestrone (E1-S) and oestradiol (E2-S). The quantitatively most important steroids present in the seminal plasma were DHEA-S, delta 5P-S and DHT-S. Vasectomy resulted in a significant but non-progressive reduction in DHT (40%) and T (23%) levels. The levels of E2, delta 5P-S and DHT-S also exhibited a smaller reduction following vasectomy. No significant changes were observed in the levels of the other steroids studied. The results are interpreted as suggesting that under normal conditions the bulk of the steroids present in the ejaculate is contributed by the accessory reproductive organs. In addition, a significant part of the DHT and T reach the ejaculate together with the sperm directly from the testis and/or epididymis. It is suggested that the normal steroid levels in seminal plasma established in this investigation could serve as reference values in the hormonal evaluation of male infertility.

Adult↗

Lack of effect of vasectomy on peripheral gonadotrophin and steroid levels.

In order to re-assess the possible hormonal consequences of male sterilization, the peripheral plasma levels of lutropin (LH) follitropin (FSH), and dihydrotestosterone sulphate (DHT-S) were measured in a group of 20 healthy men at weekly intervals in the month before and at bimonthly intervals up to 2 years after vasectomy. In addition, the levels of 14 steroids of gonadal and/or adrenal origin were measured before, and then every second month (12 subjects) or every sixth month (8 subjects) following vasectomy. No significant alterations were observed in the levels of any of the hormones studied. The results are interpreted as indicating that in the first 2 years following vasectomy in men there is no consistent or progressive change in the peripheral plasma levels of gonadotrophins or in a variety of steroids of testicular and/or adrenocortical origin.

Adult↗