Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of LHRH agonist analogs to humans reduces gonadal function through pituitary desensitization. Serum immunoreactive gonadotropin levels are modestly reduced, whereas serum bioactive LH levels are drastically suppressed. The effects on bioactive FSH levels, however, are not known. In this study, serum bioactive FSH was measured using an in vitro granulosa cell aromatase bioassay in four normal men given a LHRH agonist, [D-Trp6,Pro9-NEt]LHRH (LHRHA; 500 micrograms/day for 16 weeks), by sc infusion and testosterone enanthate (TE; 100 mg, im every 2 weeks) and in five men given 500 micrograms/day LHRHA by daily sc injection for 20 weeks and TE (100 mg every 2 weeks) from weeks 10 through 20. During the first study, serum immunoreactive FSH levels (IR-FSH) decreased by 56.5 +/- 4.8% (+/- SEM), and serum bioactive FSH (Bio-FSH) level decreased by 57.6 +/- 6.4%. The ratio of Bio-FSH to IR-FSH did not change. During the second study, both serum IR-FSH and Bio-FSH levels followed a triphasic pattern, decreasing slightly but not significantly immediately after initiation of LHRHA administration, progressively increasing to a peak (P less than 0.5 vs, baseline) at week 10, and then, after addition of TE to this regimen, decreasing slightly again. The Bio-FSH to IR-FSH ratio, as in the first study, did not change. When serum obtained at week 10 during the second study, just before initiation of TE, was chromatographed on a Sephadex G-100 column, IR-LH eluted in two distinct peaks, while IR-FSH eluted as a single peak. These results demonstrate that in normal men chronic LHRHA administration alone for up to 10 weeks or LHRHA plus TE for up to 16 weeks does not alter the qualitative characteristics of secreted FSH, since there was no dissociation between serum IR- and Bio-FSH levels.
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PMID:Maintenance of the ratio of bioactive to immunoreactive follicle-stimulating hormone in normal men during chronic luteinizing hormone-releasing hormone agonist administration. 283 9

Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 micrograms/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF-40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean +/- SEM) was 634 +/- 151 compared with 1,576 +/- 284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877 +/- 170 and 386 +/- 125 micrograms of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504 +/- 260 and 1,952 +/- 383 micrograms were secreted during vehicle and hGRF-40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF-40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.
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PMID:Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion. 286 Jan 26

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

A high incidence of luteal phase defect (LPD) has been reported using subcutaneous pulsatile gonadotropin-releasing hormone for induction of ovulation. We reviewed all patients treated with the combination of subcutaneous pulsatile gonadotropin-releasing hormone during the follicular phase and human chorionic gonadotropin during the luteal phase (GnRH-hCG) who underwent endometrial biopsy during a treatment cycle. All of these patients had biopsy-proven LPD which persisted despite traditional therapy with progesterone vaginal suppositories and/or clomiphene citrate. The mean number of biopsies out of phase per patient prior to GnRH-hCG treatment was 2.8 +/- 0.2 (+/- SEM). When treated with GnRH-hCG, 15/16 patients (94%) showed a normal endometrial biopsy. The probability of this result occurring by chance alone allowing for a 50% treatment independent correction rate is less than .001. These results show that the combination of subcutaneous pulsatile gonadotropin-releasing hormone and luteal-phase human chorionic gonadotropin can result in normal endometrial maturation in a high percentage of cycles when administered as described. It appears to be an effective alternative to traditional treatment modalities for luteal phase defect should one be needed.
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PMID:Endometrial biopsies during treatment with subcutaneous pulsatile gonadotropin-releasing hormone and luteal-phase human chorionic gonadotropin. 290 19

Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL.
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PMID:Plasma prolactin response to gonadotropin-releasing hormone during benzodiazepine treatment. 290 41

The efficacy and safety of a delayed release formulation of the LHRH agonist D-Trp6-LHRH (LHRH-A; im microcapsules) were tested in 16 girls, 0.9-8.8 yr old, and 10 boys, 2.0-10.5 yr old, with precocious puberty. All children had advanced bone age, breast or testis enlargement, and a pubertal LH response to LHRH. Precocious puberty was idiopathic in 19 subjects and secondary to a brain tumor or other central nervous system abnormality in 7. Nine girls and 6 boys had been previously treated unsuccessfully with medroxyprogesterone and/or cyproterone acetate. The microcapsules were made of 2% LHRH-A dispersed in a biocompatible biodegradable polymeric matrix of DL-lactide-coglycolide. Sixty micrograms of LHRH-A/kg BW were given im on days 1 and 21 and thereafter every 4 weeks for 10-27 months. Plasma LHRH-A levels were measured in 13 children by means of a specific RIA. On days 3, 7, 14, and 21, mean concentrations (+/- SEM) were 295 +/- 44, 218 +/- 31, 215 +/- 45, and 224 +/- 39 pg/ml, respectively. In girls, breast enlargement disappeared, and mean uterus size decreased from 44.4 +/- 2.5 to 38.1 +/- 3.1 mm (mean +/- SEM; P less than 0.02) within 6 months. Mean ovary length decreased from 23.0 +/- 1.5 to 16.2 +/- 1.5 mm (P less than 0.01). In boys, mean testis volume decreased from 8.1 +/- 1.2 to 6.7 +/- 1.2 ml (P less than 0.02) within 6 months. In both sexes, growth velocity decreased significantly, and bone maturation was generally reduced. Plasma levels of estradiol or testosterone and FSH levels decreased significantly within 3 weeks. The LH response to LHRH was reduced to normal prepubertal values after 7 weeks. No secondary clinical or biochemical escape occurred. In 1 boy, all biological features of puberty recurred within 1 month after omission of the fifth injection. No side-effects occurred, except for transient vaginal bleeding in girls after the first or second injection. No antibodies to LHRH-A were detected in the patients' sera. This study demonstrates the ability of a delayed release formulation of LHRH-A to achieve stable levels of the drug in plasma for at least 21 days after a single im injection and to suppress pituitary and gonadal secretion and pituitary response to LHRH for as long as 2 yr after therapy. This treatment appears to be more efficient in treating both clinical and biochemical abnormalities than does treatment with inhibitory steroids. Additionally, the method of administration is more practical and ensures better patient compliance.
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PMID:Long term treatment of male and female precocious puberty by periodic administration of a long-acting preparation of D-Trp6-luteinizing hormone-releasing hormone microcapsules. 293 59

The effect of a potent agonistic analog of LHRH, D-Trp6-LHRH, on hyperprolactinemia induced by sulpiride was studied in normal men. Six men received sulpiride (100 mg, twice daily, orally) for 44 days. D-Trp6-LHRH was given sc during the last 2 weeks of sulpiride administration; the dose was 500 micrograms on the first day and 100 micrograms daily for the subsequent 14 days. All men had high serum PRL levels before D-Trp6-LHRH administration (mean +/- SEM, 56 +/- 9 ng/mL), which decreased significantly after the first dose of the analog (45 +/- 5 ng/mL; P = 0.031) and also after 15 days of analog administration (41 +/- 6 ng/mL; P = 0.016). These data demonstrate that administration of LHRH agonist can inhibit the hyperprolactinemic effect of sulpiride, suggesting a direct action of the analog on the pituitary gland to modulate PRL secretion.
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PMID:D-Trp6-luteinizing hormone-releasing hormone inhibits sulpiride-induced hyperprolactinemia in normal men. 295 94

Suppression of gonadal sex steroid secretion in children with central precocious puberty (CPP) by LHRH analogs affords an opportunity to study sex steroid modulation of GH and somatomedin-C (Sm-C) secretion and to examine the role of GH and Sm-C in pubertal and prepubertal statural growth. Nocturnal serum GH and plasma Sm-C levels were measured in 10 preadrenarchal girls [mean age, 3.0 +/- 0.6] ( +/- SEM) yr with CPP before and during 2 yr of LHRH analog-induced gonadal suppression. Their mean height velocity, initially 4.6 +/- 0.6 ( +/- SEM) SD above the mean for chronological age, decreased to -0.1 +/- 0.4 SD during 12-24 months of ovarian suppression (P less than 0.00005). The mean peak nocturnal plasma GH level was 22.5 +/- 5.4 ( +/- SEM) micrograms/L during puberty, and it decreased to 10.2 +/- 2.1 micrograms/L after 3 months of suppression of gonadarche. This decrease persisted throughout the 2 yr of gonadal suppression (P less than 0.05). The reduction in GH secretion was accompanied by a decrease in mean plasma Sm-C levels from 3.5 +/- 0.7 to 1.5 +/- 0.2 U/mL after 3 months of suppression of gonadal sex steroids, which persisted during 2 yr of gonadal suppression (P less than 0.01). Suppression of ovarian function in girls with CPP results in decreased height velocity. This slowing of growth occurs in association with decreased nocturnal serum GH and plasma Sm-C levels, suggesting that acceleration of growth during puberty is partially mediated by sex steroid-induced augmentation of GH secretion.
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PMID:Changes in growth and serum growth hormone and plasma somatomedin-C levels during suppression of gonadal sex steroid secretion in girls with central precocious puberty. 296 86

The purposes of this study were to investigate the effect of a superactive agonistic analog of gonadotropin-releasing hormone, nafarelin, on uterine leiomyomas and to assess the use of magnetic resonance imaging in monitoring uterine and myoma size. Eleven women with uterine leiomyomas were treated with 800 micrograms of nafarelin per day for 6 months. Serum gonadotropin and estradiol concentrations were suppressed during treatment. The mean +/- SEM serum luteinizing hormone level decreased from 11.1 +/- 1.4 to 5.6 +/- 0.42 mlU/ml and follicle-stimulating hormone from 9.5 +/- 0.66 to 7.5 +/- 0.72 mlU/ml by 3 months of treatment (p less than 0.01). The estradiol level decreased from a pretreatment follicular phase mean +/- SEM of 43 +/- 8.3 to 19.8 +/- 3.1 (p less than 0.05) and 14.8 +/- 2.2 pg/ml (p less than 0.01) at 3 and 6 months of treatment, respectively. Mean pretreatment androgen levels (testosterone, androstenedione, and dehydroepiandrosterone sulfate) were low in these women and did not change significantly during treatment. Ten women had magnetic resonance imaging, which provided excellent resolution of individual uterine myomas. As assessed by magnetic resonance imaging, the largest myoma decreased in size in nine of 10 women; the mean decrease was 46% +/- 9%. Uterine volume decreased in all 10 patients; the mean decrease was 57% +/- 7%. In several women myomas reenlarged after discontinuance of nafarelin treatment. Posttreatment myomectomy was carried out in four women; there was minimal blood loss and no surgical complications. These data indicate that suppression of ovarian estrogen production with nafarelin is associated with a decrease in uterine myoma size in many women but that myomas may regrow with reinstitution of ovarian function. Magnetic resonance imaging is an excellent method by which to monitor treatment as changes in the size of the uterus, as well as individual myomas, can be assessed. The optimal use of gonadotropin-releasing hormone analogs may be in perimenopausal women or as presurgical treatment to decrease uterine and myoma size to facilitate myomectomy.
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PMID:Use of an agonistic analog of gonadotropin-releasing hormone (nafarelin) to treat leiomyomas: assessment by magnetic resonance imaging. 296 87

Copper, complexed to histidine (CuHis), stimulates LHRH release from explants of the median eminence area (MEA). To gain further understanding of the mechanism of copper action, in this study, we assessed the Na+ and energy requirements for CuHis stimulation of LHRH release. MEA explants, obtained from adult male rats, were incubated at 37 degrees C for 15 min with 100 microM CuHis and then for 45 min in CuHis-free medium (Krebs-Ringer-phosphate buffer, pH 7.4). LHRH released into the medium was evaluated by RIA. When the incubation buffer contained 143 mM Na+, CuHis stimulated the release of LHRH from a basal level of 17.2 +/- 1.26 (mean +/- SEM, n = 7) to 74.5 +/- 6.2 pg/60 min per MEA. When [Na+] was reduced to 16 mM Na+ (by substituting with Li+), CuHis-stimulated LHRH release was inhibited by 80% (p less than 0.001); indicating a requirement for Na+. In addition, we found that CuHis-stimulated LHRH release was a saturable function of Na+ concentration; saturation achieved with about 100 mM Na+. To assess the requirement for Na+ transport, we evaluated the effect of 1 mM ouabain, 10 microM tetrodotoxin (TTX), or 100 microM amiloride on CuHis stimulation of LHRH release. Ouabain inhibited CuHis stimulation of LHRH release by 80%, whereas TTX and amiloride were ineffective. In addition, we observed that CuHis did not stimulate LHRH release when incubation was carried out at 4 degrees C or at 37 degrees C in the presence of 5 mM KCN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Copper stimulation of LHRH release from median eminence explants. III. A process dependent on extracellular sodium. 302 98


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