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Biomedical subjects

H Kuhl

Publications and source records attributed to H Kuhl.

At least 109 records · Page 6Linked to original sources
PubMed1987

Direct radioimmunoassay of free testosterone in the evaluation of androgenetic manifestations in women.

The determination or calculation of the non-protein bound fraction of testosterone in serum had been suggested to be superior to the measurement of total testosterone levels in the evaluation of women with clinical signs of hyperandrogenism. We therefore compared the serum concentrations of free testosterone, as determined directly by radioimmunoassay, with the levels of various serum parameters in 317 women with hirsutism or acne. Total testosterone was elevated in 33%, free testosterone in 59%, and DHEA-S in 65% of the patients. Among the women with high levels of free testosterone, 24% showed serum concentrations both of total testosterone and SHBG within the normal range, indicating that the calculation of the testosterone:SHBG ratio (free androgen index) would be of limited value for androgen diagnostics. Serum free testosterone correlated positively with total testosterone and negatively with SHBG. No significant correlation was found between DHEA-S and free or total testosterone, and between total testosterone and SHBG. The stimulation of the adrenal cortex by ACTH resulted only in a significant rise in 17 alpha-hydroxyprogesterone levels. During the dexamethasone suppression test there was a significant suppression of the serum concentrations of total and free testosterone, DHEA-S, and 17 alpha-hydroxyprogesterone, while SHBG did not change. In several of the women with normal testosterone levels, free testosterone decreased by more than 50%, although the suppression of total testosterone was only slight. This was possibly due to the suppression of adrenal androgens which may compete with testosterone for the binding sites of SHBG. The direct measurement of free testosterone appears to be a valuable approach to the evaluation of women with androgenetic manifestations.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Improved enrichment of functionally intact anterior pituitary cells by sequential centrifugal elutriation and density gradient sedimentation.

By centrifugal elutriation and subsequent Percoll density gradient centrifugation, we obtained highly enriched cell populations of the anterior pituitary of ovariectomized adult rats. Enrichment of somatotrophs, gonadotrophs and mammotrophs was 90%, 80% and 77%, respectively (determined by immunocytochemistry). 41% of the GH-cells showed a medium cell size and the highest density. 52% of the LH-cells and 44% of the FSH-cells were found within the population of the large and medium-dense cells. 69% of the prolactin-cells belonged to the small-sized cells with low density. Thyrotrophs were found within all of the size ranges. The majority of the corticotrophs (82%) showed a small cell size. The enriched somatotrophs, LH-gonadotrophs, and mammotrophs responded to GRF, LRH and TRH. Before and after enrichment, somatotrophs and mammotrophs showed the same responsiveness to releasing hormones. In contrast, enriched LH-gonadotrophs exhibited a higher responsiveness to LRH than unfractionated LH-gonadotrophs.

Animals↗
PubMed1985

A randomized crossover comparison of two low-dose contraceptives: effects on serum lipids and lipoproteins.

The effect of a triphasic combination of ethinyl estradiol and levonorgestrel upon various lipoprotein parameters was compared to that of a preparation that contained ethinyl estradiol and desogestrel on days 6, 11, 21, and 28 of a control cycle, the third cycle of treatment with either ethinyl estradiol/levonorgestrel or ethinyl estradiol/desogestrel (11 volunteers each), the third cycle of a 3-month washout period, and the third treatment cycle after crossover change of the preparations. Significant increases were found in total triglycerides (15% to 20%) and phospholipids (8%) with both preparations, whereas total cholesterol and lipoprotein Lp(a) were not altered. High-density lipoprotein triglycerides (50% to 60%) and high-density lipoprotein-3 cholesterol (10% to 15%) were elevated by both contraceptives, high-density lipoprotein cholesterol and alpha-lipoprotein cholesterol only by ethinyl estradiol/desogestrel (11%), whereas high-density lipoprotein phospholipids, high-density lipoprotein-2 phospholipids, high-density lipoprotein-3 phospholipids, and high-density lipoprotein-2 cholesterol were not influenced. Both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel increased apolipoproteins A (14%), A-I (20% to 30%), and A-II (25% to 35%) significantly. Very low-density lipoprotein triglycerides were elevated (30%) only by ethinyl estradiol/desogestrel, and low-density lipoprotein phospholipids (20%) by both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel, whereas the other parameters, very low-density lipoprotein phospholipids, very low-density lipoprotein cholesterol, pre-beta-lipoprotein cholesterol, low-density lipoprotein triglycerides, low-density lipoprotein cholesterol, beta-lipoprotein cholesterol, and apolipoprotein B, were not significantly changed. Provided that the assumption is correct that high low-density lipoprotein cholesterol and apolipoprotein B and low high-density lipoprotein subfractions and apolipoprotein A are associated with an elevated risk of atherosclerosis, the results seem to represent beneficial rather than deleterious side effects of the low-dose oral contraceptives.

Adult↗
PubMed1985

A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic parameters: I. Effects upon sexual hormone levels.

The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon serum levels of endogenous sexual hormones was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was no significant suppression of serum LH and FSH during treatment with EE/NG and EE/DG except on Day 21, while estradiol levels were significantly lowered. Similar to the gonadotropin concentrations, the estrogen levels showed great individual variations; although they were depressed in the majority of the women, there was a considerable stimulation of follicular activity in 36% of the women under EE/NG and 18% under EE/DG. Both EE/NG and EE/DG suppressed significantly serum progesterone, testosterone, and DHEA-S, while prolactin was unaffected. In three cases an escape ovulation seemed to have occurred, but no pregnancy was observed. The spottings (8/22 women) and breakthrough bleedings (6/22 women) did not correlate with the serum levels of estradiol. The results indicate that the suppression of gonadotropin secretion during treatment with low-dose OC is a time-dependent process which in some women may be at or below the threshold of safe ovulation inhibition.

Adult↗
PubMed1985

A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic serum parameters: II. Effects upon thyroid function, gastrin, STH, and glucose tolerance.

The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon thyroid function and some other biochemical serum parameters was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was a significant increase (13%) in basal glucose level during treatment with both OC, but no change in glucose tolerance. Both the EE/NG and FE/DG preparation elevated serum T4 (40%), FT4 (15-22%), T3 (17-28%), and TBG (20%) significant, whereby the effect was more pronounced during the second treatment period after washing-out. The effective thyroxine ratio (ETR) was slightly (4%) but significantly increased. Contrary to this, the levels of FT3, reverse T3 (rT3), TSH, and gastrin were not altered. STH showed great individual fluctuations, but was significantly elevated by 50% during treatment with both OC. There was no effect of endogenous estradiol upon thyroid or other parameter, even though it was raised considerably in some women under OC. Although the increase in T4 and T3 is probably due to a rise in estrogen-induced TBG production, the data seem to indicate that there is a slight but effective stimulation of thyroid function during treatment with low-dose OC.

Adult↗
PubMed1985

Functional integrity of anterior pituitary cells separated by a density gradient.

Using a continuous Percoll density gradient, endocrine cells of the anterior pituitary were separated. The cells were obtained from adult female Sprague-Dawley rats which had been ovariectomized for 7 days. The gradient revealed two equally sized populations of cells with densities of about 1.02 and 1.09 g/ml. Ninety-two per cent of the cellular GH content, 64% of LH, and 60% of TSH were found in the high density peak. Sixty-one per cent of the cellular Prl appeared in the low density peak. Immunocytochemical staining of the LH containing cells showed that 74% of the gonadotrophs were in the high density peak. After separation, the cells retained their responsiveness to LRH, TRH and GRF. Culture conditions influenced stimulated hormone release. Before stimulation, the cells were cultured either in tissue culture flasks (attached cells) or in Petri dishes (cells in suspension) for 3 days. After TRH-stimulation, suspended thyrotrophs released more TSH than attached thyrotrophs. Comparing the cells of both peaks, attached thyrotrophs of the high density peak showed higher stimulated TSH-release than those of the low density peak. The response of the gonadotrophs and somatotrophs to stimulation did not differ when culture conditions were changed. The present results demonstrate that the secretory activity of endocrine cells is influenced by culture conditions and should be evaluated fore each cell type.

Animals↗
PubMed1985

Dose- and time-dependent effects of a dimeric ethynodiol-testosterone depot-preparation in female rat.

The time- and dose-dependent effects of a dimeric ethynodiol-testosterone ester upon intact and hemi-castrated female rats were compared to those of equivalent doses of norethisterone enanthate plus testosterone enanthate. In intact rats, serum LH was markedly suppressed for at least 8 weeks after a single i.m. injection of 10 or 20 mg of the dimer which exceeded the depot-effect of the combination of the enanthates. A biphasic time-and dose-dependent effect of the dimeric ester upon ovarian and uterine weight was observed. During first 2 weeks following the injection there was a pronounced enlargement of corpora lutea and a marked enhancement of progesterone secretion, probably due to a direct stimulation by the androgens. At the same time, the uteri were markedly enlarged. During the following weeks, the ovaries became progressively smaller and showed degenerative changes, the steroid levels decreased and the uteri became atrophic. When hemi-castrated rats were injected once with 1 and 5 mg of the dimer, LH became suppressed, and the compensatory hypertrophy of the ovary was inhibited. At higher doses, the weight of the ovary and uterus was increased, and the luteal function was stimulated. The results indicate that, even though the gonadotropins are suppressed, there is possibly a direct stimulatory effect of high doses of the intact dimeric molecule upon the uterus, while the stimulation of the corpus luteum function is due to an interference of the transiently elevated testosterone level with ovarian steroid biosynthesis.

Animals↗
PubMed1984

Time- and dose-dependent alterations of basal and LH-RH-stimulated LH-release during treatment with various hormonal contraceptives.

The dose- and time-dependent effect of treatment with estrogen and progestogens on serum LH before and 15 min. after the i.v. injection of 150 ng LH-RH was investigated in intact female rats. The animals were injected s.c. daily with ethinyl estradiol (EE), levonorgestrel (NG), desogestrel (DG), norethisterone (NET), chlormadinone acetate (CMA) or cyproterone acetate (CPA) alone or in various combinations, and LH was measured after 1, 2, 3, and 4 weeks of treatment and 2 weeks after termination of the injections. The treatment with low- and high-dosed combined preparations caused a marked decrease of basal LH levels which was not reversed 2 weeks after discontinuation. The combination of 30 and 50 micrograms EE with 125 or 250 micrograms NG was more effective in depressing LH-RH-induced LH release than that with 125 or 250 micrograms DG which were, however, reversible in all cases. The increase in the estrogen dose intensified the suppressive effect to a greater extent than the doubling of the progestogen dose. The suppression of the LH-RH-stimulated LH release occurred in a time-dependent manner; there was, however, a transitory amplification after 1 week when 50 micrograms EE/125 micrograms DG were tested. The high-dosed combinations of 50 micrograms EE with 500 micrograms NG, 2 mg NET, 2 mg CMA or 2 mg CPA brought about a very strong blockade of both basal and LH-RH-induced LH secretion which persisted 2 weeks after termination of treatment. The results indicate that even minor alterations in the doses of the estrogen and progestogen components of combined oral contraceptives (OC) may lead to considerable differences in the functional stage of the gonadotrophs which also depend on the duration of treatment.

Animals↗
PubMed1984

Contraception with an LHRH agonist: effect on gonadotrophin and steroid secretion patterns.

Chronic treatment with the LHRH agonist D-Ser(TBU)6-LHRH (1-9)-EA (buserelin) has been suggested as a contraceptive method since it has been shown to inhibit ovulation. To elucidate the mechanism of this paradoxical action, we investigated the pattern of gonadotrophin and steroid secretion after the daily intranasal application of 300 micrograms of the agonist. Ten volunteers with ovulatory cycles received the analogue from Day 1 to Day 22 and 5 mg norethisterone acetate from Day 16 to Day 22. Blood samples were taken on Day 1, 15, and 21 every 15 min for 6 h after the application of the agonist. LH secretion was increased nine-fold on the first treatment day as compared to Day 2 of the preceding control cycle. Thereafter, it decreased slowly but was still elevated five-fold on Day 21 of treatment. FSH release increased three-fold on Day 1 but decreased thereafter to values similar to those of the controls. During treatment with the analogue, the LH/FSH ratio changed from 1.3 (controls) to 3.8 on Day 1 and to 5.5 on Day 15 and 21 of treatment. Although the ovary retained follicular activity, ovulation was inhibited in every treatment cycle. This seemed to be due to an impairment of follicular steroid synthesis as indicated by a significant increase of 17 alpha-hydroxyprogesterone and testosterone levels for several hours after the application of the analogue. It appears that at least during the first treatment cycle of daily administration of buserelin the abolishment of pulsatile gonadotrophin release, and the abnormally increased ratio of LH/FSH secretion may possibly impair follicular maturation and thus contribute to the inhibition of ovulation.

17-alpha-Hydroxyprogesterone↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1980

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↗
PubMed1980

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↗