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Biomedical subjects

R Rolland

Publications and source records attributed to R Rolland.

143 records · Page 8Linked to original sources

Demonstration of a specific receptor for prolactin in porcine granulosa cells.

Porcine granulosa cells and subcellular fractions from these cells have been shown to have a specific receptor for ovine prolactin (OPRL). Ovine growth hormone demonstrated 7% of the potency of OPRL in displacing 125I-OPRL from its binding site; FSH, TSH, LH, insulin and ACTH showed negligible cross-reactivity. Scatchard analysis of the displacement curves suggested that 125I-OPRL has a high affinity for its receptor with a dissociation constant (Kd) for the granulosa cell-receptor of 7.4-7.7 times 10(-10) M with no change as the follicle enlarges. In contrast, the specific binding of prolactin decreased markedly with maturation of the follicles with an apparent decrease in binding sites/cell from 555 in small follicles to 300 in large (preovulatory) follicles. The demonstrated Kd's were within the range of prolactin concentrations easily attained in vivo and were in good agreement with values obtained in our laboratory and elsewhere for the prolactin receptor from mammary gland and other tissues. Consequently, these studies may provide a basis for a better understanding of the role of prolactin in ovarian function.

Animals↗

Effects of pond water, sediment and sediment extract samples from New Hampshire, USA on early Xenopus development and metamorphosis: comparison to native species.

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine.

Animals↗

Short- and long-term hormonal effects of a single dose of 50 mg tamoxifen administered to normal males.

To five potentially fertile males, a single dose of 50 mg tamoxifen was administered orally to explore the short- and long-term hormonal effects on the hypothalamic-pituitary-gonadal axis. Blood specimens were obtained through an integrated sampling technique for the first two hours after the intake of the drug. Then, samples were taken daily throughout one week, and twice weekly for the next two weeks. Hormone measurements of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and oestradiol were obtained by specific RIA. All the subjects showed different response patterns. No general characteristic of the hormonal changes in the investigated group could be given. A consistent correlation between the within-individual levels of gonadotrophin and sex steroid changes could not be observed. It is concluded, within the limits of the used experimental design, that in healthy males a single administration of tamoxifen does not result in consistent changes in serum levels of either gonadotrophins or sex steroid hormones.

Adult↗

Long-term, pulsatile, low dose, subcutaneous luteinizing hormone-releasing hormone administration in men with idiopathic oligozoospermia. Failure of therapeutic and hormonal response.

In four normal men with a history of long standing infertility, severely disturbed sperm qualities (determined in at least three spermiograms), normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (measured over a time period of 90 minutes), and lack of evidence of further andrological or other obvious endocrine disorders the effectiveness of luteinizing hormone-releasing hormone (LH-RH) treatment was investigated. LH-RH was administered subcutaneously with a portable, comterized infusion pump (Zyclomat) for 3 months, with administration intervals of 90 minutes and bolus dosages of 5 micrograms (three patients) and 20 micrograms (one patient). Semen qualities during and after LH-RH treatment, as compared to pretreatment values, showed no improvement in volume of ejaculate, number of sperms per milliliter and motility. During or at the end of the treatment period no evident differences were observed in serum LH, FSH and testosterone levels (measured over a 90 minutes period) compared with hormonal values before LH-RH therapy, nor at the low-dose (5 micrograms) neither at the high-dose (20 micrograms) administration schedule. It is concluded that pulsatile subcutaneous LH-RH treatment in normogonadotropic, oligozoospermic men does not seem to improve the therapeutical arsenal.

Adult↗

Effect of lower versus higher doses of tamoxifen on pituitary-gonadal function and sperm indices in oligozoospermic men.

Administration of the antiestrogen tamoxifen for one month to 12 patients with idiopathic oligozoospermia significantly increased the mean basal testosterone (T) level and the responses of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to constant luteinizing hormone releasing hormone (LHRH) infusion but did not significantly influence the mean oestradiol (E2) levels or the E2 over testosterone ratio. Mean sperm concentration and total sperm output increased by about 70% after a mean treatment period of 5.5 +/- 0.4 months. No statistically significant difference was found between the two subgroups of patients treated with either the lower (5 or 10 mg once daily) or higher dose of tamoxifen (10 mg twice daily) with respect to basal or LHRH stimulated gonadotropin and testosterone response or the E2/T ratio and the effect on sperm density and total sperm output. In both subgroups the sperm motility and morphology remained unchanged. In conclusion higher doses of tamoxifen in this study prove not to be superior to lower doses in improving mean sperm density and total sperm output. The relative small percentage of patients achieving normalisation of only these sperm parameters pleads for further search for more effective selection of patients and other more effective treatment modalities in patients with idiopathic oligozoospermia.

Dose-Response Relationship, Drug↗

Effect of chronic aromatase inhibition by delta 1-testolactone on pituitary-gonadal function in oligozoospermic men.

Aromatase inhibition by delta 1-testolactone (Teslac, 500 mg twice daily) for 6 months in 9 patients with idiopathic oligozoospermia lowered the levels of serum estradiol (E2) and thereby sex hormone binding globulin (SHBG) (rS = +0.40, p less than 0.025) to values -35 and -25%, respectively, below the pretreatment values (P less than 0.001 and less than 0.005). The E2 decrease was accompanied by a temporary increase (+50%) in the levels of follicle stimulating hormone (FSH), not of luteinizing hormone (LH), and of 17 alpha-hydroxyprogesterone (17 alpha-OHP), but less of testosterone (T) (+30%), which led to a transient rise in the 17 alpha-OHP/T ratio. The T/E2 ratio and "free T" index (T/SHBG) almost doubled until the end of the treatment period. During delta 1-testolactone treatment the mean sperm density gradually rose from 8.1 +/- 1.3 (SEM) before to 21.3 +/- 6.7 X 10(6)/ml after 6 months (P less than 0.01), whereas the total sperm count almost threefold increased (P less than 0.05). Sperm concentrations exceeding 20 X 10(6)/ml were achieved in 4 of the 9 patients. Two of these patients' wives became pregnant. Although the data point to a pivotal role of estrogens in the pathogenesis of the spermatogenic lesion in some patients with idiopathic oligozoospermia, the lack of a beneficial effect of estrogen lowering in others points to a multicausal nature of the disease entity.

Adult↗

Testicular steroid response to continuous and pulsatile intravenous luteinizing hormone-releasing hormone administration in normal men.

In 18 healthy normal men Leydig cell response was examined following intravenous luteinizing hormone-releasing hormone (LH-RH) administration under standardized conditions. The same total amount of LH-RH was administered for 3 hours both in a continuous (1 microgram/min; C (1,1)) and in a pulsatile fashion, by giving a 20 micrograms dose at 20 minutes intervals, P (20, 20), and a 60 micrograms dose at 60 minutes intervals, P (60, 60). Following the different modes of LH-RH administration which all caused 3-4 fold elevations of the mean endogenous luteinizing hormone (LH) concentrations and 1.7-2 fold elevations of the mean follicle-stimulating hormone (FSH) serum levels, an overt increase of the mean testosterone (T) levels was noticed up to 1.5 X the baseline value. No difference was observed in the total amount of T release among the investigated groups. The patterns of the T response, however, clearly differed from one another with a rapid increase, during the C (1, 1) and the P (20, 20) LH-RH administration, and a delayed but persistent T increase in the P (60, 60) experiment. The mean 17-hydroxyprogesterone (17-OHP) concentrations demonstrated a similar course to T in the P (60,60) experiment, while significant increases of the oestradiol (E 2) levels were never observed in all three experiments. In view of the comparable LH and FSH increments in response to LH-RH administration in either experiment the differences in T responses may be explained by assuming a direct effect of LH-RH on Leydig cell steroidogenesis in the men.

17-alpha-Hydroxyprogesterone↗

Environmental neurotoxic effects: the search for new protocols in functional teratology.

Large quantities of a number of man-made chemicals with the potential to disrupt the developing endocrine and nervous systems in wildlife and humans have been released into the environment. These chemicals are particularly damaging during the embryonic, fetal, and early postnatal periods because they resemble or interfere with the hormones, neurotransmitters, growth factors, and other signaling substances that normally control development. The effects are in many cases irreversible and often are expressed as changes in function rather than as obvious birth defects or clinical diseases. Functional changes pose challenges in documenting the extent of the lesion, especially in the case of neuroendocrinological damage. In the past decade, researchers have added new dimensions to their research strategies in order to compensate for these difficulties. The new approaches reveal more about the extent of the distribution of and exposure to chemicals that interfere with the endocrine and nervous systems and strengthen the links between exposure and damage in developing wildlife and humans. Based on this new knowledge, opportunities abound for extensive multi-disciplinary research involving developmental neurotoxicity.

Animals↗

Effects of testicular irradiation on stem cell survival, hormonal environment and spermatogenic cells in Wistar rats.

Adult male Wistar rats were exposed to 3.0 Gy local testicular irradiation. Testes of irradiated and non-irradiated rats were examined histologically and flow cytometrically, at several intervals up to 78 days after irradiation. Concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone determined at these intervals were not different from those of controls. The survival of stem cells were measured 11 weeks after irradiation (with doses varying from 1.0 Gy to 6.0 Gy at 0.6 Gy/min) by means of the repopulation index and by the number of haploid cells (spermatids). Correlation between both methods and relation to stem cell survival were discussed. The dose response curves yielded D0 values of stem cell survival of 2.33 +/- 0.06 Gy (repopulation index) and 2.08 +/- 0.08 Gy (number of haploid cells). The D0 value of the rat was not much different from that found in mice. It was concluded that the used parameters can offer insight when studying hormonal substances during irradiation.

Animals↗

Semen quality and frequency of smoking and alcohol consumption--an explorative study.

OBJECTIVE: To study the contribution of smoking and alcohol consumption to semen quality. DESIGN: Retrospective analysis. SETTING: University-based fertility clinic. PATIENTS AND METHODS: Smoking and alcohol consumption were investigated in a control group (68) and in a group of 47 subjects with defined poor semen quality (PSQ). The control group was composed of subjects whose semen showed a greater than 60% morphological normality, a greater than 60% motility with a linear progression, and a density of greater than 20 million spermatozoa/mL. The group with PSQ was composed of subjects whose semen showed a less than 30% morphological normality, less than 60% motility, characterized by slow, weak motility, and a density of less than 20 million spermatozoa/mL. Medical dossiers were studied regarding the life style of the subjects. RESULTS: The distribution of heavy smokers and light smokers did not differ statistically between the groups. There appeared to be a higher, but statistically insignificant, proportion of heavy smokers in the PSQ group (50%) compared to the control group (32.3%; P < .1); nor were significant differences found between cases and controls with respect to alcohol consumption pattern. In the PSQ group, a comparison of the semen characteristics of the daily drinkers with those of all the other subfertile patients showed no statistical difference concerning semen volume (4.1 +/- 1.9 vs. 3.3 +/- 1.3 mL; P > .1), sperm density (10.6 +/- 7.8 vs. 8.9 +/- 5.8 million spermatozoa/mL; P > or = .1), and percentage of motile spermatozoa (27.0 +/- 15.1 vs. 25.5 +/- 16.1%; P > .1). However, a lower percentage of normal sperm morphology was observed in the daily-drinker group (17.6 +/- 7.2% vs. 23.0 +/- 6.5% for the other subfertile patients; P < .05). CONCLUSION: Factors such as smoking and alcohol consumption do not seem to play a pivotal role in the etiology of poor semen quality, but a pattern of excessive alcohol consumption may decrease further an already low percentage of sperm with normal morphology.

Adult↗

A randomised study to compare the efficacy and safety of new 17 beta-oestradiol transdermal matrix patch with Estraderm TTS 50 in hysterectomised postmenopausal women. The Lyrelle Study Group.

This study was designed to compare the efficacy and safety of two sizes of Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50, a reservoir system. Three hundred and ninety-four (394) hysterectomised postmenopausal women between 30 and 65 years of age participated in this open-label, randomised, multicentre clinical trial. The main efficacy criterion was the reduction in the mean number of hot flushes per day at six months. Secondary efficacy end points included other climacteric symptoms as well as various psychofunctional and genitourinary disorders. A significant decrease from baseline in the mean number of hot flushes/day was observed in all three groups from the end of cycle 1, reaching 90% at the end of cycle 7. there was no statistically significant difference between Lyrelle 50 and Estraderm at any time point for any parameter; however, between-group differences between Lyrelle 80 and Estraderm for various parameters were seen in the first three cycles in favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all three groups, without significant between-group differences. We conclude that the new Lyrelle patch is a highly effective system for transdermal oestrogen replacement therapy that may enhance long-term patient compliance.

Administration, Cutaneous↗