Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland.
The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21-23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
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Parenti
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Cocchi
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Ceresoli
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Marcozzi
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Müller
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D006160:Guanosine Triphosphate; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine