"Medical oophorectomy" using a long-acting GNRH agonist--a possible new approach to the treatment of endometriosis.

Five women with endometriosis were given a daily dose of a potent long-acting GnRH agonist, D-Trp6-Pro9-Net-LHRH (GnRH-A) for 28 days in an attempt to suppress ovarian estrogen secretion. The mean level of estradiol (E2) during sampling over 24 hours decreased (P less than 0.01) from 62 +/- 11 to 10 +/- 1 pg/ml at the end of treatment.

Direct inhibition of testicular steroidogenesis and gonadotrophin receptor levels by [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH, potent agonists of GnRH.

The effects of [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH on testicular function in rats was evaluated. In adult rats the administration of 0.01, 0.

Introduction of rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector: expression and regulation.

We have introduced the rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector. The ability of the viral DNA to induce foci in the recipient cells was used as a dominant selection marker. Several copies of rat growth hormone DNA were integrated in the mouse cells.

In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function.

Several tetrahydroisoquinolines (TIQs) were tested for their in vitro and in vivo capacities to modulate prolactin (PRl) and beta-endorphin (beta-end) secretion by the rat pituitary and for their abilities to displace [3H]spiroperidol and [3H]naloxone binding from pituitary and hypothalamic membranes. Receptor binding studies showed that TIQs could be classified as having (a) higher affinity for opiate receptors (tetrahydropapaverine, papaverine, 6-methylsalolinol, 1-carboxysalsolinol and 3',4'-deoxy-norlaudanosolinecarboxylic acid), (b) higher affinity for the dopamine receptor (salsolinol and 7-methylsalsolinol), or (c) approximately equal affinity for the two binding sites (6,7-dimethylsalsolinol and tetrahydropapaveroline, THP). In freely moving male rats, THP produced a several-fold increase in plasma PRL levels.

Calcitonin COOH-terminal cleavage peptide as a model for identification of novel neuropeptides predicted by recombinant DNA analysis.

A strategy is presented for identification of putative neurohormones that were predicted by sequence analysis of recombinant cDNa molecules. The nucleotide sequence of a cloned calcitonin cDNA insert predicts that the proteolytic excision of calcitonin from a 136-amino acid precursor should generate two additional peptides derived from regions flanking the calcitonin sequence on the NH2 and carboxyl termini. The predicted 16-amino acid COOH-terminal cleavage peptide (NH2-Asp-Met-Ala-Lys-Asp-Leu-Glu-Thr-Asn-His-His-Pro-Thr-Phe-Gly-Asn-COOH) was chemically synthesized using solid phase procedures.

Superfusion of dissociated pancreatic islet cells attached to Cytodex beads.

Pancreatic islets of neonatal were dissociated by collagenase and cultured for 3 days in the presence of Cytodex beads to allow attachment of the cells to these microcarriers. The bead-attached cells were packed in columns and superfused with a low bicarbonate medium using the same method that we had originally developed for dissociated anterior pituitary cells of the rat. The secretion of insulin, somatostatin, and glucagon by the cells was monitored by radioimmunoassays.

Specific high affinity binding sites for somatostatin-28 on pancreatic beta-cells: differences with brain somatostatin receptors.

Saturable and high affinity binding sites have been obtained for an iodinated somatostatin-28 (SS-28) analog, [Leu8,D-Trp22,125I-Tyr25] SS-28, in a membrane preparation from hamster insulinoma, mainly composed of pancreatic beta-cells. Specific binding is maximal after 1 hour incubation at 22C and represents 65% of the total binding. KD for [Leu8,D-Trp22,Tyr25] SS-28 is 0.

Interaction of gonadotropin-releasing hormone agonist and antagonist with progesterone, prolactin, or human chorionic gonadotropin during pregnancy in the rat.

Two GnRH analogs, one agonist and one antagonist, have been administered to pregnant female rats with or without concomitant treatments with progesterone (Po), PRL, or hCG. During the first week of gestation, Po was consistently capable of totally reversing the deleterious effect of the agonist, while PRL and hCG were slightly less effective. During the second week of pregnancy, only Po and hCG were effective.

Corticotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption.

Corticotropin-releasing factor administered intracerebroventricularly produces prolonged elevation of plasma concentration of epinephrine, norepinephrine and glucose. These hormonal changes are associated with an increase in motor activity and oxygen consumption. No change in body temperature is observed.

In vivo corticotropin-releasing factor-induced secretion of adrenocorticotropin, beta-endorphin, and corticosterone.

A 41-residue peptide purified as a corticotropin-releasing factor/beta-endorphin-releasing factor (CRF) in vitro was tested for its ability to stimulate the secretion of ACTH, beta-endorphin, and corticosterone in three animal groups: 1) unanesthesized rats bearing indwelling venous cannulae, 2) rats pretreated with chloropromazine plus morphine sulfate plus pentobarbital (CPZ-MS-Nb, and 3) rats with hypothalamic deafferentiations in the frontal and lateral retrochiasmatic areas. In all three bioassays iv administration of 0.1-10 micrograms CRF elicited a dose-related increase in plasma ACTH and beta-endorphin values over a 5- to 15-min period.

Intermittent long-term administration of a potent gonadotropin-releasing hormone agonist in normal men.

The effects on pituitary-gonadal function of the potent gonadotropin-releasing hormone agonist D-trp6-pro9-n-ethylamide-LHRH (LRFA), 50 micrograms subcutaneously every 4th day for 10 weeks, were evaluated in seven normal men. A modest rise in mean serum LH levels was noted during the treatment period. Mean serum FSH levels were unchanged.

Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report.

The uncoupling of pituitary stimulation and response observed in adults during administration of the luteinizing hormone-releasing hormone analogue, D-Trp6-Pro9-NEt-LHRH (LHRHa) suggested that this drug might be useful in treating precocious puberty. We treated five girls with idiopathic precocious puberty (ages two to eight) for eight weeks with daily subcutaneous injections of LHRHa. The patients had Tanner II to IV pubertal development, advanced bone age, an estrogen effect on vaginal smear, measurable basal gonadotropin levels with pulsed nocturnal secretion, and a pubertal gonadotropin response to LHRH.

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2.

Effect of lesions in the periventricular nucleus of the preoptic-anterior hypothalamus on growth hormone and thyrotropin secretion and brain somatostatin.

Two experiments were performed to study the role of somatostatin (SRIF) neurons of the preoptic-anterior hypothalamic area (PO-AHA) in regulating growth hormone (GH) and thyrotropin (TSH) secretion in rats. Small lesions were placed in the periventricular (PV) zone and blood was collected at 24 h and 15 days after surgery. Blood samples were obtained at 3 min and at 15 min after ether exposure for assessing non-stress levels, respectively, of plasma GH and TSH.

Primary structure of corticotropin-releasing factor from ovine hypothalamus.

Sequence analysis was performed of an ovine hypothalamic 41-residue polypeptide that had been postulated to be a putative corticotropin-releasing factor (CRF) because of its high intrinsic corticotropin releasing activity. The NH2-terminal 39 residues of CRF were determined by Edman degradation of 0.6-3.

The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.

The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule.