Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats
J. Kamegai et al., Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats, J NEUROENDO, 11(4), 1999, pp. 299-306
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.