Release of growth hormone by TRH in intact rats or in intact or hypophysectomized rats bearing a heterotopic pituitary.
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Biomedical subjects
Publications and source records attributed to V Locatelli.
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Intrajugular administration of LHRH (0-6 and 1-2 mug) in hypophysectomized rats which received renal grafts of anterior pituitary induced a small but significant rise in plasma GH 5 and 10 min post-treatment. LHRH, at the same dose levels, was ineffective in weight-matched intact controls. MIF, at the dose of 1-2 mug, induced a slight GH rise 5 min after treatment in hypophysectomized trasnplanted rats, while it was ineffective in intact controls. Unlike the two hypothalamic peptides, alpha-MSH (0-6 and 1-2 mug) was ineffective as a GH-releaser in both transplanted and intact rats.
12-day-old female and male pups were killed 10 min after the injection of either saline or thyrotropin releasing hormone (TRH), and plasma growth hormone (GH) and prolactin (PRL) levels were measured by radioimmunoassay (RIA). At all doses used (0.15, 0.3, 0.6 and 1.5 mug/100 g b.w.i.p.), TRH induced a significant, although not dose-related, increase in plasma GH levels, but was effective in releasing PRL only at the greatest dose level (1.5 mug/100 g b.w.). The GH-releasing effect of TRH was even more evident in 12-day-old pups subjected to central sympathectomy of 6-hydroxydopamine (6-OHDA, 60 mug/10 mul intraventricular route) 1 week before; in these animals, TRH was ineffective in releasing PRL even at the greatest dose level (1.5 mug/100 g b.w.). In pups pretreated with 6-OHDA, the GH-lowering effect of insulin hypoglycemia or cold exposure was markedly reduced, while the PRL responses were unmodified. Baseline plasma PRL levels were markedly increased following 6-OHDA administration. It is proposed that in the infant rat the greater GH than PRL responsiveness to TRH, which opposed the pattern of response present in the adult animal, may be due to the existence of a 'physiologic' functional disconnection between the central nervous system (CNS) and the anterior pituitary (AP). Results obtained following central sympathectomy by 6-OHDA, which further disrupted CNS-AP links, substantiate this view.
Intravenously administered synthetic hpGRF 1-40 at doses of 0.1, 0.33 and 1.0 microgram/kg increased plasma GH in a dose-dependent fashion in 4 normal prepubertal children. hpGRF 1-40 at the dose of 1.0 microgram/kg stimulated GH release, though to a lesser extent than in normals, in 7 children with isolated GH-deficiency (IGHD) but failed to do so in a patient with craniopharyngioma. In all normal children and 6/7 patients with IGHD, hpGRF 1-40 at all doses used induced a clear and sustained lowering of plasma prolactin levels; this effect was lacking in the patient with craniopharyngioma. hpGRF 1-40 had no effect on plasma FSH, LH, TSH or glucose levels nor did it influence pulse rate, blood pressure, or body temperature. These results indicate that hpGRF 1-40 is a potent stimulus to GH release in normal prepubertal children and holds promise for treatment of GH-deficient children. In addition, in both normal children and children with IGHD, hpGRF 1-40 is a potent suppressor of prolactin levels.
Three children with acquired immunodeficiency syndrome (AIDS) and chronic anaemia and leucopenia were treated with 5 micrograms/kg recombinant granulocyte colony-stimulating factor subcutaneously three times a week and 50 IU/kg erythropoietin subcutaneously twice a week. The therapy was not interrupted during the follow-up period. All children showed an increase of leukocyte count and haemoglobin levels. No transfusion was necessary and the number of admissions into hospital fell. These results suggest that combined therapy with granulocyte colony-stimulating factor and erythropoietin may improve leukopenia and anaemia, which is not zidovudine-related, in children who have AIDS.
Recent evidence has shown that growth hormone-releasing hormone (GHRH) enables investigation of the pathophysiology of GH secretion in a variety of different states, but it cannot be used as a test for probing pituitary somatotrophic function, due to the extreme inter- and intra-subject variability in normal subjects. This task is better accomplished when compounds which deprive the pituitary of inhibitory (somatostatinergic) influences, e.g. pyridostigmine, arginine, etc., are given in combination with GHRH. Administration of GHRH in both animals and humans reveals a state of GH hyperresponsiveness in the immediate postnatal period, which is likely to be due to a reduced pituitary sensitivity to somatostatin. GH responses to GHRH are relatively constant throughout the different stages of pubertal development, though further studies are needed to confirm these findings, and decline after the third-fourth decade in men, after menopause in women. It is apparent that during aging the releasable pool of GH is preserved and that impaired GH secretion is due to defective hypothalamic GHRH function and a relative predominance of somatostatinergic function.
Newly synthesized peptides are described which release growth hormone in the infant rat and their biological activity is compared with known GHRPs. Some of these peptides are the most potent GHRPs reported to date.