Growth Hormone‐Releasing Hormone Receptor (GNRH‐R) and Growth Hormone Secretagogue Receptor (GHS‐R) mRNA Levels During Postnatal Development in Male and Female Rats

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Abstract
Experimental evidence suggests that differential pituitary sensitivity to hypothalamic signals exerts a role in mediating both age and sex dependent patterns of growth hormone (GH) release and synthesis. One mechanism by which pituitary sensitivity to hypothalamic 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 of receptors for two known stimulators of GH release, growth hormone‐releasing hormone (GHRH) and the synthetic peptidyl and non‐peptidyl GH secretagogues (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 examined the age‐ and sex‐dependent expression of the GHS‐R in whole hypothalamic extracts, since the GHS‐R is also expressed in a variety of nuclei within the hypothalamus and has been linked to central regulation of the GH‐axis. Pituitary GHRH‐R mRNA concentrations were age‐dependent; the highest levels were observed in d1 pituitaries and then declined with age, reaching a nadir by d30. These results are in concordance with the age‐related decline in pituitary GHRH sensitivity. In contrast, the ontogenic pattern of GHS‐R expression was bimodal; GHS‐R mRNA concentrations in d1 and d30 pituitaries 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 levels were comparable in males and females within each age while GHS‐R mRNA levels were gender dependent. At d30, male GHS‐R mRNA levels were ≈30% greater than in their female counterparts. This was reversed at d75, when females had 89% more GHS‐R mRNA per pituitary and 65% more per somatotrope than did age‐matched males. These sexual differences further support a role for gonadal steroids in the modulation of pituitary GHS‐R synthesis. The ontogenic and gender‐specific pattern of hypothalamic GHS‐R expression differed from that observed for the pituitary. Hypothalamic GHS‐R mRNA levels increased with age but exhibited no significant sex difference at each age tested. Taken together, these data demonstrate that changes in the levels of pituitary GHS‐R mRNA, but not GHRH‐R mRNA, are associated with changes in the gonadal steroid environment, thereby implicating the GHS/GHS‐R signalling system as a control point in the establishment and maintenance of sexually dimorphic patterns of GH secretion.