Biomedical subjects
Publications and source records attributed to H D Taubert.
A sequential regimen of 100mg of clomiphene citrate (days 5 to 9) and 180 mug of ethynyl estradiol or 7.5 mg of conjugated estrogens (days 10 to 16 or 17) was given to 29 infertile patients. Eleven patients conceived. Four pregnancies terminated as early abortions; the remaining seven went to term. In four cases an ovarian hyperstimulation syndrome developed.
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Dimeric and trimeric oestradiol derivatives were administered as single subcutaneous injections into ovariectomized rats and the duration of oestrogenic effect was determined by means of daily vaginal smears. It could be shown that these preparations have a very protracted oestrogenic effect, and their threshold dose is considerably higher as compared to monomeric oestradiol diacetate. A dimeric compound containing one free hydroxy group caused a relatively even response in all animals with a linear relationship between the logarithm of dose and the duration of action. The effect was even more protracted when fully esterified dimeric or trimeric oestradiol succinates were used, but occurred in a more scattering manner. The duration of effect of 40 mug of the trimeric compound exceeded that of the equivalent dose of oestradiol undecylate. It is conceivable that the depot-effect of these oestradiol derivatives is due to delayed elimination.
The dose of 15 IU PMSG was found to be optimal for inducing ovulation within 74 hours in 27-day-old immature female rats. There was a significant decrease in the mean number of ova per ovulating animal when the dose was raised beyond this (r = 0.6554, p less than 0.001 for the range from 15 to 100 IU), but the number of ovulating animals did not decrease unless more than 80 IU PMSG were injected. The PMSG-induced ovulation was not affected by treating the animals with 10 or 100 mug clomiphene citrate at 0, 24, 48, 54, 60, 66 hours or at 0, 24, and 48 hours.
An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range.
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Eleven women with amenorrhoea after taking oral contraceptives were studied. A clomiphene stimulation test was performed in ten, with six also having an LH-RH stimulation test. In most of them there was no reaction or a severely impaired response to both clomiphene and LH-RH, but bleeding episodes could be provoked in most women by continuing clomiphene treatment, and some of these ovulated when HCG was added to the therapeutic scheme. A possible relationship between preexisting psychosomatic disorders and the genesis of postcontraceptive amenorrhoea is discussed.
Serum FSH, LH and testosterone were measured in 57 (42) normal men and in 80 male infertile patients. In the former, mean (x) FSH was found to be 2.5 ng/ml with a range (x +/- 2 SD) from 0.25 ng/ml to 5.3 ng/ml, mean LH was 2.2 ng/ml with a range from 0.5 ng/ml to 5.6 ng/ml, and mean testosterone was 540 ng/100 ml with a range from 190 mg/ml to 890 ng/100 ml. Immunoassayable FSH was found to be elevated in 17 out of 42 presumably infertile males with sperm counts below 20 million/ml, and in 5 out of 12 men with sperm counts above 120 million/ml. There was no correlation between testosterone and sperm number, motility, and seminal fructose content. The concurrence of depressed spermatogenesis and elevated FSH levels seems to be a relatively good indicator for the presence of organic disorders of the testis.
The kinetics of enzymatic hydrogenation of synthetic progestogens by female rat liver microsomes with NADPH as hydrogen donor were investigated by means of an optical test. Steroids with high progestational activity (Clauberg test) showed a low hydrogenation rate (Vmax). There also seemed to be a certain correlation between molecular structure and Vmax. The metabolites from incubation with the progestogens were isolated from the micro-preparations, and identified by infrared spectroscopy. It was found that the hydrogenation of the olefinic and carbonylic groups involved the uptake of hydrogen from NADPH.
A double-antibody solid-phase radioimmunoassay for the measurement of rat LH was described. The use of a solid-phase method for the second incubation resulted in a considerable saving of time as compared to the conventional double-antibody method. The sensitivity and accuracy of the method were not affected by this modification. It was found that there was a cross-reaction between the NIAMD-anti-rat-LH-serum-1 used and NIAMD-rat-FSH-RP-1. This indicates that the test system does not specifically measure rat LH but gonadotrophic activity. The RIA was tested under different experimental conditions. In male rats, the effect of castration and of subsequent treatment with testosterone oenanthate upon serum LH, and upon the weight of the seminal vesicles, the ventral prostate, and the levator ani, was examined. Serum LH rose rapidly after castration and reached 2 to 4 weeks after orchidectomy a maximum (8-9 fold increase). Subsequent treatment with testosterone oenanthate caused a rapid decrease of serum LH. The accessory sex organs showed reciprocal changes of weight. In oophorectomized rats whose pituitaries had been blocked with oestradiol monobenzoate and progesterone, a linear log-dose response of plasma LH was found after administration of various doses of synthetic LH-RH.
The rate of hydrolysis of several aminoacyl-4-nitroanilides by rat hypothalamic arylamidases was investigated. The activity of these enzymes which were mainly found in the 105 000 times g supernatant fraction of homogenates of the hypothalamus and other parts of the brain was shown to depend upon the presence of metal ions and free thiol groups, and to be inhibited by puromycin. As previous investigations had shown that Cys-NA is an appropiate substrate for measuring hormone effects on hypothalamic arylamidases, L-cystine arylamidase and its interaction with various peptide hormones were examined in detail. It could conclusively be shown that this enzyme interacts particularly with oligopeptides. Its activity was competitively inhibited by TRF, oxytocin, lysine vasopressin, and LH-RH. It was also shown that the biological activity of LH-RH and its inhibitory effect on the hydrolysis of L-cystine-bis-p-nitroanilide decreased when it was incubated for various periods of time with the 105 000 times g supernatant of rat hypothalumus homogenate.
The effect of the intravenous administration of several hormones on L-cystine arylamidase in the hypothalamus of the rat was examined. The injection of 10 mug LH into adult male and female rats was followed within 90 min by an increase of the enzyme activity by 50%, while infantile animals were not affected. When prepuberal rats were pretreated sc with testosterone and progesterone. The iv injection of 0.1 mug oestradiol-17beta into female, and of 0.5 mug testosterone into male intact mature rats also resulted in an increase of hypothalamic enzyme activity. The maximal increase in enzyme activity was seen 16 h after steroid treatment. As it had previously been shown that L-cystine arylamidase inactivates LH-RH, it may be assumed that this enzyme is involved in the short-loop feedback of LH. This assumption is based on the observation that an elevation of plasma LH brings about an activation of the enzyme system, which subsequently leads to an increased inactivation of LH-RH in the hypothalamus. This mechanism seems to depend on the presence of certain plasma levels of oestrogen in female, and of testosterone in male animals.
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