Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats

Experimental evidence suggests that differential pituitary sensitivity to h ypothalamic signals exerts a role in mediating both age and sex dependent p atterns of growth hormone (GH) release and synthesis. One mechanism by whic h pituitary sensitivity to hypothtalamic GH regulators could be modified is by the differential synthesis of their pituitary receptors, In the present report we therefore studied the age and sex dependency of the expression o f receptors for two known stimulators of GH release, growth hormone-releasi ng hormone (GHRH) and the synthetic peptidyl and non-peptidyl GH secretagog ues (GHSs). Pituitary GHRH receptor (GHRH-R) and GHS receptor (GHS-R) mRNA levels were measured by reverse transcriptase-polymerase chain reaction (RT -PCR) in male and female rats at postnatal day 1, 10, 30 and 75, We also ex amined the age- and sex-dependent expression of the GHS-R in whole hypothal amic extracts, since the GHS-R is also expressed in a variety of nuclei wit hin the hypothalamus and has been linked to central regulation of the OH-ax is. Pituitary GHRH-R mRNA concentrations were age-dependent; the highest le vels were observed in dl pituitaries and then declined with age, reaching a nadir by d30. These results are in concordance with the age-related declin e in pituitary GHRH sensitivity. In contrast, the ontogenic pattern of GHS- R expression was bimodal; GHS-R mRNA concentrations in dl and d30 pituitari es were approximately twice those at d10 and d75. These results mirror the transient increase in GHS sensitivity observed around the onset of puberty, suggesting that gonadal steroids mediate GHS-R expression. GHRH-R mRNA lev els were comparable in males and females within each age while GHS-R mRNA l evels were gender dependent. At d30, male GHS-R mRNA levels were approximat e to 30% greater than in their female counterparts. This was reversed at d7 5, when females had 89% more GHS-R mRNA per pituitary and 65% more per soma totrope than did age-matched males. These sexual differences further suppor t a role for gonadal steroids in the modulation of pituitary GHS-R synthesi s. The ontogenic and gender-specific pattern of hypothalamic GHS-R expressi on differed from that observed for the pituitary. Hypothalamic GHS-R mRNA l evels increased with age but exhibited no significant sex difference at eac h age tested. Taken together, these data demonstrate that changes in the le vels of pituitary GHS-R mRNA, but not GHRH-R mRNA, are associated with chan ges in the gonadal steroid environment, thereby implicating the GHS/GHS-R s ignalling system as a control point in the establishment and maintenance of sexually dimorphic patterns of GH secretion.