Regulation of pituitary growth hormone-secretagogue and growth hormone-releasing hormone receptor RNA expression in young dwarf rats

Growth hormone-secretagogue receptor (GHSR) RNA is known to be expressed in the hypothalamus and pituitary. Since endogenous GH secretagogue (GHS) is still unknown, the physiological role of GHS and GHSR in growth is not well understood. In this study, we have determined the effects of growth hormon e in GH-releasing hormone receptor (GHRHR) and GHSR RNA expression in spont aneous Dwarf rats (SDRs) which are deficient in GH secretion, with or witho ut GH replacement. Twenty-five-day-old SDRs received daily s.c. injection of human GH (40 mu g /kg BW x 2/day) or control solution for two weeks. On day 40, the rats were sacrificed by decapitation and the pituitaries were immediately removed an d quickly frozen. Total RNA was extracted from the pituitary, and mRNA codi ng GHSR was detected and semi-quantitated by competitive RT-PCR. Pituitarie s from control SDRs showed strong GHSR RNA expression and the expression le vel was 5 to 10 times higher in females than in males. When GH was replaced , GHSR RNA expression greatly decreased. Pituitary GHRHR RNA expression, de termined by RNase Protection Assay, was similar in male and female control animals; and was also greatly reduced in rats treated with GH when compared to the control. These results suggest that the expression of both GHSR and GHRHR is regulated by growth hormone, presumably via changes in hypothalam ic GHRH and/or endogenous GHS. The apparent sexual dimorphism in GHSR indic ates different regulatory effects of sex steroid in young growing SDRs.