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

The hypophyseal human growth hormone (hGH), a Raben type laboratory preparation, was re-evaluated as regards its innocuity for therapeutic use. Besides the usual control tests recommended by the Romanian Pharmacopoeia, the contamination of the hGH for clinical use with acute and slow viruses, was investigated taking into account the withdrawal of this hormone in many developed countries. The contamination was absent both with acute viruses as resulted from hemadsorption on cell cultures and counterimmunoelectrophoresis, and with slow viruses as observed from a two year-follow up of guinea pigs injected intracerebrally with the hGH preparation. Further, the content of the growth hormone itself as well as the contamination degree with other pituitary hormones was examined. The hGH-RIA content was 2.23 +/- 0.13 IU/mg (means +/- SEM), range: 1.38-2.80 IU/mg (1st International Standard hGH 80/505-1982). The prolactin contamination assessed by RIA was 187.34 +/- 37.66 ng/mg hGH, range: 28.44-385.20 ng (International Standard WHO: 80/541). The LH and FSH contamination as quantified by the Isocommerz (DDR) RIA kits was with two orders of magnitude lower than 10 IU-LH/IU-hGH, the upper LH contamination limit considered as acceptable. Moreover, the proportion of the large molecular forms in the lyophilized hGH preparation was investigated by polyacrylamide gel electrophoresis. Corroborating the data obtained by these control tests with our previous experience on 149 pituitary dwarfs treated with this hGH preparation during the interval 1964-1984, resulted minor risks of some dangerous side effects of hGH administration in children with growth hormone deficiency by possible contamination with pathogenic agents or with other disturbing hormones.
 ...
PMID:Study on the innocuity of the hypophyseal human growth hormone. 251 Feb 46

There is evidence that the capacity to synthesize gonadotropins is less in teenage boys with gonadotropin deficiency (GD) than in those with constitutional delay of puberty (DP). We hypothesized that this might predispose the latter group to have a greater pituitary-testicular response to the potent long-acting GnRH agonist nafarelin. We evaluated GD patients 14.3-24.0 yr of age (n = 8) and prepubertal DP boys 14.8-17.6 yr of age (n = 3). In most subjects the response to nafarelin was compared to that of frequent nocturnal blood sampling for LH and testosterone levels. All subjects received a single dose of nafarelin (1.0 micrograms/kg, sc), and blood was then sampled at 0.5- to 4.0-h intervals for 24 h. Patients with GD could not be distinguished from those with DP by pubertal staging criteria or by baseline values of LH, FSH, or testosterone. Patients with GD exhibited no rise in plasma LH levels during sleep, in contrast to those with DP. All GD patients had LH and FSH responses distinctly less than those of the DP group between 3-24 h postnafarelin. The peak incremental responses of GD and DP to nafarelin were, respectively: LH, 5.5 +/- 2 3 (+/- SEM and 77.2 +/- 8.6 IU/L (P less than 0.02); FSH, 2.7 +/- 1.2 and 9.4 +/- 0.8 IU/L (P less than 0.005). Testosterone peak responses were lower as well (0.26 +/- 0.2 vs 1.6 +/- 0.5 nmol/L, P = 0.05). This pilot study suggests that the response to a single test dose of nafarelin distinguishes GD from DP in the teenage years as well as does measurement of nocturnal LH levels. The testosterone response to the GnRH agonist adds a new dimension to GnRH testing. Nafarelin also allows assessment of the bioactivity of endogenous gonadotropin, is a more potent stimulus of pituitary-testicular function than endogenous GnRH secretion, and is more cost-effective than nocturnal sampling.
 ...
PMID:A new test of combined pituitary-testicular function using the gonadotropin-releasing hormone agonist nafarelin in the differentiation of gonadotropin deficiency from delayed puberty: pilot studies. 252 66

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.
 ...
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

Pre-operative bilateral simultaneous inferior petrosal sinus sampling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients greater than or equal to 1.4:1 were seen for beta-endorphin (2.8 +/- 1.3, mean +/- SEM), PRL (4.2 +/- 1.3) and GH (6.9 +/- 2.4) as well as for ACTH (5.1 +/- 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and beta-endorphin were r = 0.95 (P less than 0.01), ACTH and PRL r = 0.90 (P less than 0.01) and for ACTH and GH r = 0.89 (P less than 0.05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to co-secretion of beta-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of beta-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus sampling can give information about pituitary function unobtainable from peripheral hormone levels.
 ...
PMID:Multiple pituitary hormone gradients from inferior petrosal sinus sampling in Cushing's disease. 284 95

The induction of adrenocortical special zone (S.Z.) by gonadotrophin administration was studied in male brush tailed possums. Castrated males injected with porcine FSH (NIH-FSH-P2) formed well developed S.Z.s, varying in sizes from 5-20% of the gland's volume. Pregnant mare serum gonadotrophin (PMSG) was ineffective. From adrenal homogenates of FSH treated possums incubated with [3H]-progesterone the major conversion products were 5 beta-reduced steroid metabolites (72%) and cortisol (4%). The conversion products from adrenals of saline and PMSG treated males were cortisol and corticosterone (65%). Of the ten untreated castrates, one had a well developed S.Z. and two had S.Z.s at an early stage of development. Significant 5 beta-reduction of [3H]progesterone was only found in one animal. The plasma FSH concentrations were in intact males 317 +/- 41 ng rat FSH ml-1 (mean +/- SEM) and in castrates 769 +/- 64. The possible reasons for the lack of spontaneous S.Z. formation in intact males are discussed.
 ...
PMID:Induction of adrenocortical special zone in the male possum (Trichosurus vulpecula). 288 77

Five habitual aborters without a known organic cause of their pregnancy losses were studied in detail by serial blood sampling for immunoreactive estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and the ratio of the two. All patients had premenstrual spotting regularly. Luteal phase progesterone levels on the 6th postovulatory day were significantly lower (11.8 +/- 1.2 ng/mL, mean +/- SEM) than in control patients (20.8 +/- 3.5 ng/mL, mean +/- SEM). Results of immunoreactive estrogen, FSH, and LH assays and the FSH/LH ratio did not reveal a discernible pattern of deviation from normal. Indirect immunofluorescence of blood samples from all habitual aborters showed evidence of autoimmunity in three of five patients without clinical symptoms of autoimmune disease. Treatment by superovulation produced at least one living child in each couple. The balance of pregnancy outcome changed from 100% abortion (N = 31) before treatment to 31% (N = 13) after treatment. These results suggest that treatment with superovulation may be the treatment of choice for habitual aborters with a subtle luteal phase deficiency.
 ...
PMID:Superovulation of habitual aborters with subtle luteal phase deficiency. 288 81

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.
 ...
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

beta-Endorphin (beta-EP) and methionine-enkephalin (Met-Enk) have been detected in human follicular fluid in concentrations several times higher than those in plasma. These data stimulated us to study the possible physiological role of ovarian opioids. We, therefore, determined the effects of both beta-EP and Met-Enk, alone or in combination with naloxone, on FSH-induced progesterone (P) secretion by cultured granulosa cells. Granulosa cells were collected from follicular fluid recovered at laparoscopy in seven superovulated women. The cells were preincubated with RPMI-1640 medium containing 20% fetal calf serum in 5% CO2 for 48 h, followed by the addition of 100 mU purified FSH and the various test substances for 48 more h. beta-EP (10 nM to 1 pM) had no effect on P secretion either alone or in combination with FSH and/or naloxone. Micro- to picomolar amounts of Met-Enk increased FSH-induced P secretion up to 186.9 +/- 35.1% (+/- SEM). Met-Enk had no affect in the absence of FSH, and its action was significantly blunted by the concomitant addition of 10(-5) M naloxone. These data provide evidence for a dose-dependent naloxone-reversible synergistic action of Met-Enk and FSH on P secretion by cultured granulosa cells. This finding supports the hypothesis of the existence of an ovarian opioid system.
 ...
PMID:Met-enkephalin enhances follicle-stimulating hormone-dependent progesterone production from cultured granulosa cells. 294 12

We evaluated a GnRH agonist (GnRHa) as a potential single stimulus to both pituitary and ovarian secretion in 13 girls with true precocious puberty. We compared the GnRH agonist [6-D-(2-naphthyl)alanine]GnRH acetate (nafarelin, Syntex) administered as a single sc injection of 0.2 microgram/kg to GnRH infused iv in a dose of 2 micrograms/kg X h for 3 h and assessed the response of plasma steroid intermediates in estradiol (E2) biosynthesis. Although serum LH and FSH levels increased to similar peaks 3 h after commencing GnRH and nafarelin testing, they rose faster (P less than 0.01 at 1 h) and remained elevated longer (P less than 0.05 at 24 h) after nafarelin administration. At the third hour of testing with either agent, LH and FSH rose 8.8- and 3.4-fold, respectively (P less than 0.001 vs. baseline), whereas the rise in E2 was inconsistent and averaged only one third (P less than 0.02). However, plasma E2 increased later after nafarelin, but not after GnRH, rising from a baseline level of 30 +/- 6 (+/- SEM) to 115 +/- 13 pg/ml at 24 h (P less than 0.001). The least E2 response to nafarelin at this time was 150%. This rise is probably an underestimate of the maximum E2 rise, since a 6-fold response to nafarelin was found at 12 h in patients sampled then. Measurement of steroid intermediates from progesterone and 17 alpha-hydroxypregnenolone to E2 indicated that the response to nafarelin was typical of normal ovarian follicular secretion. That is, plasma levels of the intermediates in E2 biosynthesis rose less than 2-fold, and only the elevations in androstenedione, from 58 +/- 10 to 78 +/- 16 ng/dl (P less than 0.05), and estrone, from 14 +/- 3 to 38 +/- 7 pg/ml (P less than 0.02), at 24 h were significant. The greater effectiveness of nafarelin than GnRH in stimulating E2 secretion appears to be related to the more prolonged gonadotropin response. The magnitude, consistency, specificity, and rapidity of the gonadotropin and E2 responses to nafarelin indicate that this is a promising agent for rapidly testing pituitary and ovarian function simultaneously.
 ...
PMID:The rapid ovarian secretory response to pituitary stimulation by the gonadotropin-releasing hormone agonist nafarelin in sexual precocity. 294 12

LRH and its agonists have been shown to exert both stimulatory and inhibitory effects on testicular function. In the present study, the dose and length of treatment were tested to determine the appearance of the stimulatory and inhibitory effects of LRH agonist on testicular axis including the three levels. Two doses of an agonist of LRH, 40 and 100 ng/100 g body weight (buserelin, 'agonist'), were administered daily for 1 to 15 days to adult male rats. Control rats received the vehicle only. On day 1, 2, 4, 8 and 15 of treatment, the pituitary, testicular and peripheral levels (weight of accessory sex organs and androgen receptors in ventral prostate) were tested 6 h after the last injection. For the 15 days of treatment with both doses, a stimulatory effect of the 'agonist' was observed on LH and FSH release. A short exposure (1-2 days) to the low dose of the 'agonist' had a stimulatory effect on the density of LH/hCG testicular receptors (326 +/- 49 vs control 185 +/- 21 fmol/mg protein, mean +/- SEM), on the weights of seminal vesicles and ventral prostate and exposure to both doses led to high plasma testosterone levels (13.8 +/- 0.5 and 13.7 +/- 0.7 ng/ml, respectively, vs control 2.6 +/- 0.3 ng/ml), and to an increased density of nuclear androgen receptors in the ventral prostate (142 +/- 9 and 144 +/- 15 fmol/mg protein respectively vs control 97 +/- 12 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dose and time effects of treatment with low doses of a LRH agonist on testicular axis and accessory sex organs in rats. 301 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>