Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat.
Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0.85 mg; medium dose, 1.7 mg; high dose, 3.4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 microgram human GHRH(1-29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506.0 +/- 68.5 micrograms/l), peak GH levels were enhanced by the low dose (704.4 +/- 47.8 micrograms/l, P less than 0.05), unaltered by the medium dose (543 +/- 65.8 micrograms/l) and suppressed by the high dose (312.7 +/- 55.2 micrograms/l, P less than 0.05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P less than 0.01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00-12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30-14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 microgram human GHRH(1-29) with samples taken at 5, 10, 20 and 40 min following stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Miell
J
J
Department of Medicine, University Hospital of Geneva, Switzerland.
Corder
R
R
Miell
P J
PJ
McClean
C
C
Gaillard
R C
RC
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001623:Betamethasone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology*; D007116:Immunization, Passive; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000276:immunology* / Q000494:pharmacology; D013268:Stimulation, Chemical
D000906:Antibodies; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001623:Betamethasone