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Biomedical subjects

H G Bohnet

Publications and source records attributed to H G Bohnet.

At least 37 records · Page 2Linked to original sources

Testosterone production by mouse Leydig cells is stimulated in vitro by atrial natriuretic factor.

The synthetic atrial peptides, rat atrial natriuretic peptide, atriopeptin I and atriopeptin II, stimulated testosterone production by mouse Leydig cells in a time- and concentration-dependent manner. The maximum stimulation of the steroidogenesis in response to the peptides was 6-10-fold over the basal level, as compared with 20-24-fold stimulation obtained with saturating concentrations of hCG. The stimulation of steroidogenesis by the most potent peptide, atriopeptin II, was markedly enhanced in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, suggesting an involvement of cyclic nucleotides. However, neither basal nor hCG-stimulated levels of cAMP were altered by the peptide, though testosterone production in response to submaximal concentrations of hCG was increased in the presence of atriopeptin II. The nature of the second messenger involved and the mechanism of action of the atrial peptides may be elucidated by further research in progress.

1-Methyl-3-isobutylxanthine↗

New aspects of oestrogen/gestagen-induced growth and endocrine changes in individuals with Turner syndrome.

Patients with Turner syndrome (n = 33) were subjected to a sequential oestrogen/gestagen replacement therapy (21 days 2 mg oestradiol valerate plus 0.5 mg norgestrel for 10 days) for 1-4 years. In individuals aged 12-17 years, growth velocities before treatment ranged between 2.9 and 1.9 cm/year and increased to 6.8-3.8 cm/year following sex steroid substitution for 1 year. Thereafter a decrease was observed; depending on age, pre-treatment velocities were observed within 2-4 years of replacement therapy. On average, bone age advanced 1 year following 1 year of sex steroid administration and adult bone age was reached following 2-4 years of treatment. Approximately 70% of the individuals noted breast development to stage IV according to Tanner and experienced regular withdrawal bleedings. Oral administration of oestradiol valerate resulted in serum oestradiol levels normally seen during the early follicular phase; hypergonadotropic LH and FSH levels decreased slightly following 1 year of therapy. Growth ranged between 4 and 13 cm; in the oldest individuals the final height ranged between 149 and 156 cm. In summary, the oestrogen/gestagen replacement therapy chosen for this study achieved development of secondary sex characteristics, endocrine changes, growth velocities, bone age advancement and to a certain extent growth, which was almost comparable to that observed during puberty in healthy girls.

Adolescent↗

Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death.

Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.

Adult↗

Different hormonal patterns in human menopausal gonadotropin-treated, clomiphene citrate-treated, and untreated conception cycles.

Serum concentrations of seven different hormones were analyzed during 189 singleton conception cycles. One hundred nine women were treated with human menopausal gonadotropin (hMG), 52 women received clomiphene citrate (CC), and 28 became pregnant spontaneously. Serum progesterone (P) levels in hMG-treated women started to increase on day 18 of the cycle and reached peak concentrations between days 28 and 32 of the cycle. Serum estradiol (E2) concentrations paralleled the P patterns. In hMG-treated women, there were significant correlations between serum E2 and P concentrations and the number of the mature follicles observed before ovulation (both P less than 0.01). CC-treated and spontaneous conception cycles revealed significantly lower serum levels of P, E2, testosterone, 17 alpha-hydroxyprogesterone, and prolactin, compared with hMG-treated cycles (P less than 0.05). Elevations of the gonadal steroids in hMG-treated women possibly reflect the multiple corpora lutea formed after multiple ovulations.

17-alpha-Hydroxyprogesterone↗

Treatment of hyperprolactinemic amenorrhea with Metergoline.

The ergoline derivative, Metergoline, in a dosage of 4 to 24 mg/day, was administered for one to eight months to 42 patients with hyperprolactinemic amenorrhea. Mean serum prolactin (PRL) concentrations before treatment were 91.2 ng/mL in the patients with functional hyperprolactinemia (N = 29) and 256.9 ng/mL in the patients with pituitary tumor (N = 13). Within four weeks, Metergoline treatment reduced these PRL concentrations to 39.5 ng/mL and 82.9 ng/mL, respectively. In this study Metergoline treatment resulted in restoration of menstruation in a total of 37 patients; 28 patients ovulated, and eight became pregnant. It is considerably more effective in functional hyperprolactinemia than in hyperprolactinemia caused by adenoma.

Adenoma↗

Phorbol ester stimulates progesterone production by isolated bovine luteal cells.

The tumor promoter, phorbol 12-myristate-13-acetate (PMA), is known to modulate the response of several steroidogenic tissues presumably by activating a Ca++- and phospholipid-dependent protein kinase (protein kinase C). The presence of this kinase has been demonstrated in bovine corpus luteum, although its role in steroidogenesis by these cells is unknown. We report here the effects of PMA on progesterone production by the enzymically dispersed bovine luteal cells in vitro. PMA (1-50 nM) produced a dose- and time-related increase in progesterone production by the luteal cells. The maximum stimulation was achieved with 10 nM PMA. Higher concentrations of PMA led to a decline of steroidogenesis close to the basal level. A nonpromoting derivative, 4 alpha-phorbol 12,13-didecanoate had no effect. The PMA-induced stimulation of progesterone production was not associated with a change in the cAMP level. PMA added together with suboptimal doses of human CG, 8Br-cAMP, cholera toxin, or forskolin significantly increased the amount of progesterone produced. PMA as well as human CG-induced steroidogenesis was sensitive to cycloheximide inhibition. The conversion of exogenous pregnenolone or 25-hydroxycholesterol to progesterone was not altered by PMA. We conclude that PMA at nanomolar concentrations is able to stimulate progesterone production by bovine luteal cells and that the site of action of PMA is distal to the formation of cAMP but before the formation of pregnenolone. The observed effects of PMA in luteal cells are probably linked to its ability to activate protein kinase C, since a diacylglycerol could mimic the steroidogenic action of PMA.

8-Bromo Cyclic Adenosine Monophosphate↗

Preparation and properties of human chorionic gonadotropin antagonist for biological studies: antifertility effects in the female rat.

We compared the effects of treatment of clinical grade hCG powders with anhydrous HF (hydrogen fluoride) or TFMS (trifluoromethane sulfonic acid). HF treatment yielded stable product (DG-hCG), which had desirable antagonistic activity in mouse Leydig cells. Binding of HF-hCG to ovarian granulosa cell FSH receptors was less than 5% as compared to purified ovine FSH. As LH/hCG receptor specificity was not significantly compromised crude hCG could be directly used in obtaining large amounts of the antagonist. The effects of antagonist (DG-hCG) and agonists crude hCG and purified hCG were evaluated in pregnant rats. When administered between days 1 to 5 of pregnancy, crude DG-hCG inhibited serum progesterone and oestradiol levels and implantation. The effect was dose-dependent. However, both crude hCG and purified hCG elevated progesterone level and partially inhibited implantation (up to about 40%). In the post-implantation period (days 8-11) crude DG-hCG treatment induced abortion due to a decrease in circulating progesterone and oestradiol levels. The agonists, crude hCG and purified hCG, on the other hand, elevated both steroid levels in serum and induced partial termination of pregnancy (up to 50%). During the second half of pregnancy, when luteotropic support of LH becomes unnecessary in the rat, crude DG-hCG (antagonist) had no effect on parturition. However, crude or purified hCG caused delay in parturition by sustaining high level of progesterone in circulation. Our data demonstrate that the antifertility effects of crude DG-hCG are more potent and consistent than the administration of either crude or purified hCG in the pregnant rat.

Abortifacient Agents↗

Unexplained infertility and its treatment with intermittent GnRH application.

Spontaneous LH fluctuations were estimated in patients with unexplained infertility. This suggested that irregular LH bursts and a slightly decreased frequency are present in these individuals. Administration of sex steroids suppressed LH serum levels and no LH pulses were noted thereafter. Intermittent GnRH application by means of an automatic pump (Zyklomat) induced regular LH fluctuations: follicular maturation was enhanced using 20 micrograms GnRH per pulse than with 10 micrograms; the former dose however appeared to be supra-physiological. Three pregnancies occurred in these patients who had not conceived following previous treatment with clomiphene and human menopausal gonadotropins.

Dosage Forms↗

Prolactin concentrations in follicular fluid following ovarian hyperstimulation for in vitro fertilization.

Prolactin (PRL) and sex steroid concentrations were measured in follicular fluids of women treated either with (1) clomiphene/hCG or with (2) clomiphene + hMG/hCG. Method 1 of ovarian stimulation resulted in lower follicular PRL and higher oestradiol-17 beta (E2) and progesterone (P) concentrations than method 2. There was no difference in the PRL and sex steroid concentrations of follicles with fertilized and of those yielding unfertilized ova, but in both stimulation types, follicles from which no oocytes were obtained had high PRL and low E2 and P levels. Significant positive correlations were evident for PRL and T and E2 and P, respectively, while PRL and P were negatively correlated.

Chorionic Gonadotropin↗

Prolactin secretion during pregnancy and puerperium: response to metoclopramide and interactions with placental hormones.

Prolactin (PRL) response to an intravenous administration of metoclopramide (10 mg) was examined during normal pregnancy and puerperium. Basal PRL and the metoclopramide-induced increase of PRL increased gradually during pregnancy. This was paralleled by serum estradiol, estriol, and progesterone levels. A positive correlation between serum progesterone and metoclopramide-induced PRL concentrations was found at week 36 of pregnancy. In lactating women, metoclopramide always induced higher increases of PRL than did suckling stimulation on the seventh day postpartum. The PRL responses to suckling and metoclopramide were significantly correlated with each other, but no correlation was found between placental steroid levels throughout pregnancy, PRL levels after parturition, and total milk production during seven days postpartum.

Animals↗

[Diagnostic value of the prolactin stimulation test in infertile women with galactorrhea].

In infertile women breast secretion may be provoked in approximately 11%, although basal prolactin serum levels are only elevated (greater than 12 ng/ml) in 30% of the cases. This casts doubt on the diagnostic value of a single determination of prolactin serum concentrations in women with galactorrhea and/or infertility. Introduction of a dynamic function test of prolactin secretion into the endocrine work-up of such patients improves our diagnostic tools as can be seen by the fact that approximately two thirds of the patients with galactorrhea exhibited an exaggerated response of prolactin to metoclopramide despite normal baseline levels of prolactin.

Female↗

Phorbol esters inhibit LH stimulated steroidogenesis by mouse Leydig cells in vitro.

The effect of phorbol esters on the stimulation of testosterone production in response to LH was studied in mouse Leydig cells incubated in vitro. The tumor promoting phorbol esters, Phorbol-12-myristate-13-acetate and Phorbol-12-13-didecanoate at nanomolar concentrations effectively inhibited testosterone production by Leydig cells in response to stimulation by LH, whereas non-tumor promoting phorbol esters were ineffective. When the cells were stimulated by 8Br-cAMP, instead of LH, the testosterone production was stimulated similarly as in the presence of LH, but phorbol esters were without any effect. This suggests that the tumor promoting phorbol esters may act in the Leydig cells by suppressing the stimulation of cAMP production in response to hormonal activation and/or by interfering with the hormone-receptor interaction.

8-Bromo Cyclic Adenosine Monophosphate↗

Preliminary report about a modified gonadotropin (human menopausal gonadotropin/human chorionic gonadotropin) treatment in infertile patients with premature luteinization.

Premature luteinization is a frequent phenomenon observed in infertile women undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) therapy for corpus luteum insufficiency or anovulatory cycles. By inducing hyperprolactinemia in these women with sulpiride, we intended to create a dysfunctional state in these women, which supposedly induces a better reaction to hMG/hCG therapy. The rationale behind this combined treatment was the observation that hyperprolactinemic amenorrheic patients have a much higher pregnancy rate under hMG/hCG treatment than the above group. Three cases are reported in detail, illustrating the altered ovarian response to combined sulpiride-hMG/hCG treatment. Of 60 infertile women with repeated premature luteinization, 12 conceived after sulpiride-hMG/hCG therapy. Their expected pregnancy rate would have been very low (5% or less) if conventional hMG/hCG treatment had been continued.

Adult↗

Oxytocin and vasopressin have no effect on progesterone production and cyclic AMP accumulation by rat luteal cells in vitro.

Enzymically dispersed luteal cells obtained from PMSG-hCG-treated immature pseudopregnant rats were incubated with oxytocin and vasopressin. In response to increasing doses of hCG the rat luteal cells produced progesterone and accumulated intracellular cAMP in a dose-dependent manner. A neuropeptide GnRH agonist (4 X 10(-6) M) produced a significant inhibition of hCG-stimulated progesterone production and of accumulation of intracellular cAMP. However, neither the basal nor the hCG-stimulated rate of progesterone production and level of intracellular cAMP was affected by the neurohypophysial peptides tested. Therefore, it is concluded that oxytocin and vasopressin do not have a direct action on steroidogenesis by rat luteal cells.

Animals↗