Alterations of adenylyl cyclase-coupled growth hormone-releasing hormone (GHRH) pituitary receptors in different conditions of GHRH deprivation.
Previous studies have clearly shown that the progressive decrease of growth hormone (GH) secretion occurring during ageing is coupled with a reduced responsiveness of pituitary GHRH receptors both in terms of GH secretion and activation of the adenylyl cyclase (AC), in the presence of increased basal values of the enzyme. The mechanism(s) subserving the age-associated alterations of GHRH-sensitive AC is likely related to the progressive decrease of hypothalamic GHRH function occurring with ageing. In this context, in old male rats, short-term administration of GHRH decreased the high basal AC activity and enhanced the GHRH-stimulated AC activity. Along this line, we decided to investigate whether experimentally induced abrogation of GHRH function in adult rats would induce the same alterations of AC-coupled GHRH receptors present in aged rats. Passive immunization of male young-adult rats with supra-maximal doses of GHRH antiserum (Ab-GHRH) significantly reduced the AC responsiveness to GHRH, an effect already evident 5 days post-injection and still present at 10 days. At this time interval, the treatment also evoked a significant increase of basal AC levels and of Gs alpha protein in the pituitary and completely blocked the GH-releasing effect of a bolus injection of GHRH. Furthermore, mechanical disruption of brain-pituitary links by complete stereotaxical ablation of the mediobasal hypothalamus induced a significant increase of basal AC levels and Gs alpha protein in the pituitary and a strikingly lower AC responsiveness to GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)
Qing
Y
Y
Department of Pharmacology, University of Milano, Italy.
Parenti
M
M
Guzzi
F
F
Ceresoli
G
G
Müller
E E
EE
Cocchi
D
D
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D013007:Growth Hormone-Releasing Hormone / Q000172:deficiency* / Q000378:metabolism* / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000502:physiology; D007106:Immune Sera / Q000276:immunology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
D007106:Immune Sera; D011956:Receptors, Cell Surface; D011388:Prolactin; D013007:Growth Hormone-Releasing Hormone; D000262:Adenylyl Cyclases