Search PubMed⌕ Search

Biomedical subjects

H D Taubert

Publications and source records attributed to H D Taubert.

At least 55 records · Page 3Linked to original sources

The effect of sex steroids and hormonal contraceptives upon thymus and spleen on intact female rats.

In view of a possible influence on oral contraceptives upon the immune system, the effect of chronic treatment of intact adult female rats with sex steroids and contraceptive preparations upon the thymus and the spleen was investigated. Daily injections with 10 micrograms estradiol, estradiol benzoate, or diethyl stilbestrol for 2 weeks resulted in a marked but reversible involution of the thymus, while the spleen was not affected. Androgens exerted a significant effect at a dose of 0.3 mg, and progestogens only when 2 mg were given. When various contraceptive preparations were injected for 4 weeks, there was a total involution of the thymus which persisted even 2 weeks after cessation of treatment. The effect appeared to be mainly due to the estrogenic component. Progestogens intensified the reduction of thymic weight only at higher doses. Histological examinations revealed that estrogen treatment alone resulted in a reduction of the cortex and a depletion of lymphocytes. When contraceptive preparations were administered, the medulla was also reduced, and both cortex and medulla were replaced by reticular and adipose tissue. The estrogen receptors of thymus cytosol showed dissociation constants between 0.34 and 0.49 nM in diestrous rats, progesterone-treated rats and ovariectomized rats, and binding capacities between 6.5 and 2.6 fmoles/mg protein. It remains, however, to be shown whether the estrogen-induced involution of the rat thymus may lead to an impairment of immune responses.

Androgens↗

Synthesis and release of gonadotropins: effect of an oral contraceptive.

A double-stimulation test with 100 micrograms gonadotropin-releasing hormone per dose given twice within two hours was carried out in eight normally cyclic women before and during treatment with a combined oral contraceptive (30 micrograms ethinyl-estradiol + 150 micrograms desogestrel). The test was performed on days 8 to 11, 19 to 22, and 24 to 27 of a control cycle, and during the first and third treatment cycles. This oral contraceptive was found to diminish the capacity of the gonadotropes for the synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to a higher degree than that for the acute release in each treatment cycle. During the treatment-free interval, the reaction of LH differed from that of FSH: while the release of the former remained suppressed, that of FSH did not differ from the control cycle.

Adolescent↗

Serum levels and pharmacokinetics of norethisterone after ingestion of lynestrenol: its relation to dose and stage of the menstrual cycle.

The peak concentration, peak time, the area under the serum concentration time curve (AUC) and half-life of serum norethisterone (NET) after a single application of lynestrenol (LYN) to female volunteers demonstrated that 0.7 mg NET is bioequivalent to 1 mg LYN which is rapidly converted to NET. There was a decrease of the peak values and an increase of half-life of NET during the periovulatory and luteal phase which was, however, not significant due to the great individual differences. The shift of the peak time to longer intervals and the increase of half-life of NET after ingestion of higher LYN doses indicate a certain limitation of the metabolic capacity of the liver. One of the volunteers who complained of nausea and vertigo after the administration of 5 mg LYN, showed the highest serum values of NET. The large interindividual variations of the serum levels of synthetic steroids demonstrate a possible risk of contraceptive safety in women with low steroid levels and possibly a coherence between extremely high serum levels of synthetic steroids and side effects.

Adult↗

[The significance of alpha-feto-protein (AFP) and human chorionic gonadotrophin (HCG) during the first half of pregnancy (author's transl)].

The determination of AFP and HCG was used as a diagnostic parameter for the functional integrity of the feto-placental unit during the first 20 weeks of normal and disturbed pregnancies. In contrast to HCG which can already be detected very shortly after nidation and reaches a maximum between the 10th and 12th week of gestation, AFP does not begin to rise discernibly before the 8th and 9th week and attains the highest values in the third trimester. The assay of AFP did not contribute relevant data when carried out before the 10th week of pregnancy. Contrary to that, an irreversibly damaged pregnancy has to be expected when lower than normal AFP values are found after the 10th week, even in the presence of a normal level of HCG. Likewise, higher than normal values should be taken as a reliable sign of embryonal demise after the 14th week of pregnancy, as long as a multiple gestation, a previous amniocentesis or a neural tube defect can be excluded. Serum AFP did not only increase markedly in many cases after interruption of pregnancy, but even after amniocentesis or premature rupture of the amniotic sac when fetal cells having a high content of AFP enter the maternal circulation.

Abortion, Spontaneous↗

Augmentative and inhibitory effects of chronic steroid injections on LH release and their dependency on time.

The effect of daily s. c. injections of 50 micrograms ethinyl estradiol, 1 mg norethindrone and of 1 mg megestrol acetate upon basal and LH-RH-stimulated LH release was investigated in intact female rats. Basal serum LH was rapidly depressed by ethinyl estradiol and norethindrone, while megestrol acetate was less effective. the pituitary response to 30 or 150 ng LH-RH was initially augmented by the treatment with norethindrone reaching a maximum after 5 days, by ethinyl estradiol with a maximum after 10 days, and megestrol acetate after 20 days. In every case, the positive effect was followed by inhibition of H-RH mediated LH release when treatment with the respective steroid was continued. Two weeks after discontinuing of the daily injections, the blockade of the pituitary was abolished. It is concluded that a rapid decrease of endogenous LH-RH release is responsible for the suppression of basal serum LH, while a concomitant direct action on the pituitary augments the response to exogenous LH-RH during the first days of steroid application. When the treatment with steroids is continued for a prolonged period of time, the pulsatile pattern of LH-RH release from the hypothalamus becomes impaired, and this results in dependency on the type of steroid in inhibiting of pituitary response.

Animals↗

The mechanism of action of a new low-dosed combined oral contraceptive.

The effect of a new low-dosed combined oral contraceptive (OC) containing 37.5 microgram ethinyl estradiol and 0.75 mg lynestrenol (Ovoresta M) upon gonadotropin release and follicular activity was studied in two groups of normally cyclic women. When the administration of the OC was started on day 1 of the cycle, the normal pattern of gonadotropin secretion was disrupted, and the midcycle LH and FSH peak was abolished. The mean level of LH and FSH was somewhat lower than in normal cycles, but the difference was not significant. In one case, serum estradiol rose to the level of the normal cycle indicating follicular activity. Even though there was a rise in serum estradiol to normal values when the OC was started on day 10 of the cycle (in 4/5), both the midcycle LH and FSH surge and ovulation were suppressed (in 3/4). The pituitary response to 100 microgram LH-RH on day 21 was impaired. The LH-response correlated significantly with the serum estradiol concentration. In summary, the low-dosed OC exerts its effect by interfering with follicular ripening and inhibiting the preovulatory LH surge.

Adult↗

Ovulation inhibition by daily i.m. administration of a highly active LH-RH analog (d-ser(TBU)6-LH-RH-(1-9)-nonapeptide-ethylamide).

A highly active LH-RH-analog (D-Ser(TBU)6-LH-RH-(1-9)-nonapeptide-ethylamide = HOE 766) was administered to normally cyclic and ovulatory women in a double-blind study. Each woman received from day 1 through day 14 of the cycle according to a randomization plan either 10 microgram HOE 766 i.m. or a placebo. Ovulation was inhibited for at least two weeks in all subjects receiving HOE 766. The initially very marked release of LH measured 4 hourse after the injection decreased within 3 days by approximately 50%, and remained at this level for the remainder of the experiment while the initially high FSH response was abolished during further treatment. In 3 out of 5 women receiving the analog, serum estradiol was severely suppressed, in the remaining 2 slightly. Within 5 days after the discontinuation of treatment, the pituitary had regained the capacity to respond normally to LH-RH. It is postulated that follicular maturation is disturbed by the unphysiologic pattern of gonadotropin secretion during administration of HOE 766.

Adult↗

Competition of various LH--RH analogs and fragments with 135I-LH--RH for specific binding sites on isolated pituitary plasma membranes.

The displacement by various LH--RH analogs and fragments of 125I-LH--RH specifically bound to plasma membranes isolated from rat anterior pituitaries was investigated. The addition of increasing amounts of unlabelled LH--RH resulted in an increasing displacement of bound 125I-LH--RH. When some fragments of LH--RH or of an analog with little biological activities were incubated, a much weaker affinity for LH--RH binding sites could be observed. No correlation between biological effectiveness and binding affinity was, however, found when several highly active LH--RH analogs were tested. The potent analogs competed much less efficiently for specific binding sites on isolated plasma membranes than LH--RH. Binding experiments with iodine-labelled (D-Ser(But)6-LH--RH(1--9)-nonapeptide-ethylamide indicated that the small binding affinity of the superactive analog may be due to a lower association rate while the dissociation rate is comparable to that of LH--RH. Contrary to LH--RH, no binding equilibrium was reached during 2 h of incubation of the analog with plasma membranes. The physiological role of LH--RH binding sites on isolated pituitary plasma membranes remains to be elucidated.

Animals↗

[Early diagnosis of molar pregnancy by measuring AFP and HCG in serum (author's transl)].

In 3 women with the histologically confirmed diagnosis of molar pregnancy (in one case dizygote), the time-course of the concentration of HCG and AFP was measured in serum prior to expulsion and curettage, respectively. Serum HCG was found to be in the normal range of monozygotic and dizygotic pregnancies. Contrary to that, serum AFP was lower than normally seen and showed a tendency to decline even further. This seems to indicate that AFP is a valuable diagnostic adjunct to the determination of serum HCG in the diagnosis of disturbances of early pregnancy characterized by embryonic demise (molar pregnancy, blighted ovum), as it is a parameter of fetal integrity rather than that of normal trophoblastic function.

Chorionic Gonadotropin↗

[Rapid radioimmunological test for HCG in normal and disturbed early pregnancy (author's transl)].

The clinical evaluation of a rapid radioimmunological test for HCG in serum showed that this method is as suitable as conventional radioimmunoassay or receptor methods in the diagnosis of normal and disturbed early pregnancy. Using a direct immunosorbent method total time requirements for the estimation could be reduced to half a working day. Sera of 314 women with normal pregnancies showed an exponential increase of HCG concentrations in serum during the first 8 weeks and thereafter steady levels for several weeks. As the anti-HCG serum used has only a slight cross reactivity with LH, false-positive results need hardly be expected in states of high LH levels in serum (menopause, polycystic ovaries, preovulatory LH peak). HCG concentrations in serum were clearly diminished in all pregnancies ending in abortion and in nearly all extrauterine pregnancies. Repeated estimations in early pregnancy enable a diagnosis of ectopic or disturbed intrauterine pregnancy to be made before symptoms of rupture, haemorrhage and similar complications occur.

Abortion, Spontaneous↗

Enzyme kinetic studies and inhibition by oligopeptides of LH-RH degradation in rat hypothalamus and pituitary.

The enzyme kinetic parameters of the degradation of luteinizing hormone-releasing hormone (LH-RH) and L-cystine-bis-(4-nitroanilide) (Cys-NA) by rat hypothalamic (HYP) and pituitary (PIT) extracts and the effect of various oligopeptides on the rate of LH-RH inactivation were investigated in vitro. The 105,000 x g supernatant of 1 rat HYP inactivated 57 microgram LH-RH during a 30 min incubation (Km = 12.4 microM, V max = 2.33 microgram LH-RH/mg protein/min), and of one rat anterior PIT, 48 microgram LH-RH during 30 min of incubation (Km = 12.2 microM, V max = 8.0 microgram LH-RH/mg protein/min). The synthetic substrate Cys-NA competitively inhibited LH-RH degradation with a Ki of 8.5 microM in the HYP and 6 microM in the PIT enzyme preparation. Vice versa, LH-RH also competitively inhibited the cleavage of Cys-NA with inhibition constants of 14 microM (HYP) and 15 microM (PIT) indicating that the 2 substrates are probably cleaved by the same enzyme. The most effective inhibitors of LH-RH degradation were found to be angiotensin-related peptides, neurotensin, bradykinin, and bacitracin. A relatively weak effect was obtained with oxytocin, enkephalin and puromycin. It is concluded that endogenous oligopeptides such as angiotensins, neurotensin, bradykinin, etc., may possibly influence H-RH degradation in the PIT and the HYP. The synthetic substrate Cys-NA may be an appropriate substrate for measuring the activity of an LH-RH-degrading peptidase, which therefore could be classified as arylamidase.

Aminopeptidases↗

The biological activity of dimeric testosterone, a new long-acting androgen, and of testosterone enanthate in the castrated male rat.

The long-term effect of single intramuscular injections of various doses of dimeric testosterone and of testosterone enanthate into castrated male rats upon serum testosterone, luteinizing hormone (LH), pituitary LH, and on the weight of the seminal vesicles, the ventral prostate and the levator ani muscle, was investigated. The effect of the enanthate was characterized by a rapid onset and a protracted androgenic action and a suppression of serum LH, while the dimeric testosterone brought about only a moderate but very even depot effect. The injection of 5 mg of the dimeric testosterone caused a positive feedback effectu upon LH release for 16 weeks. The results indicate that the dimeric testosterone may exert is hormonal effects as intact ester.

Animals↗

Effect of sex hormones on HL-RH-degrading hypothalamic enzyme system during estrus cycle in rats.

Basal activity of L-cysteine arylamidase, an LH-RH-degrading enzyme, was determined in the hypothalamus of rats at 4 h intervals throughout the 4-day estrus cycle. The activity of the enzyme system fluctuated during the four estrus stages in a circadian rhythm with maximal values in the night and lowest values at noon. The injection of increasing doses of estradiol-17 beta at various estrus stages caused a moderate stimulation of enzyme activity with no relationship to endogenous hormone levels or estrus stage. The highest activation of the hypothalamic enzyme in response to the application of progesterone occurred at such periods of the cycle when endogenous plasma progesterone is known to be low, and vice versa. When luteinizing hormone or prostaglandin E2 were injected i. v. during the various estrus stages maximal stimulation could be observed at diestrus. The LH-RH-degrading L-cystine arylamidase in the hypothalamus of the rat seems to play a modulating role in the regulation of the tonic LH release during the estrus cycle, but apparently does not influence the events governing the preovulatory LH-peak.

Aminopeptidases↗