SEX-RELATED ALTERATIONS IN HYPOTHALAMIC GROWTH HORMONE-RELEASING HORMONE MESSENGER-RNA BUT NOT SOMATOSTATIN MESSENGER-RNA-EXPRESSING CELLS IN GENETICALLY-OBESE ZUCKER RATS

The possibility that the growth hormone (GH) suppression associated wi th obesity is due to alterations in hypothalamic GH-releasing hormone (GHRH) and/or somatostatin (SRIH) has been considered, but the data ar e not consistent, In the present study, we sought to clarify the roles of GHRH and SRIH in obesity by using in situ hybridization to localiz e and quantify the level of expression of GHRH mRNA- and SRIH mRNA-con taining neurons in the hypothalamus of male and female lean and obese Zucker rats (12 weeks of age n = 6 per group). In lean animals, the nu mber of GHRH mRNA-expressing cells in the arcuate nucleus and SRIH mRN A-containing neurons in the periventricular nucleus was 2- to 3-fold h igher in males compared to females. The obese phenotype in the male wa s associated with a striking reduction in arcuate GHRH mRNA expression , both in terms of number of cells (-71%; p < 0.01) and grains/cell (- 44%; p < 0.05), In contrast, in obese females, there was a marked augm entation (+175%; p < 0.05) in the number of GHRH mRNA-containing cells in the arcuate nucleus compared to their lean littermates. The small population of GHRH mRNA-containing neurons of the ventromedial nucleus was not modified in male obese rats, while it was considerably increa sed (p < 0.05) in obese females. Neither the number or labeling densit y of SRIH mRNA-containing neurons in the periventricular and arcuate n uclei of obese rats of either sex was changed when compared to their s ex-matched lean counterparts. These results demonstrate that: (1) the obese male Zucker rat exhibits a marked diminution in hypothalamic GHR H mRNA expression, while a reverse pattern is evident in the obese fem ale; (2) hypothalamic SRIH mRNA-containing neurons are not significant ly altered in obese rats of both sexes. Our findings suggest that the impaired GH secretion of the obese Zucker rat is due, at least in part , to alterations in hypothalamic GHRH gene expression and that SRIH do es not play a major role.