ONE CLASS OF GROWTH-HORMONE (GH) RECEPTOR AND BINDING-PROTEIN MESSENGER-RIBONUCLEIC-ACID IN RAT-LIVER, GHR(1), IS SEXUALLY DIMORPHIC AND REGULATED BY GH

In the rat, alternatively spliced messenger RNA (mRNA) species encode GH receptor (GHR) and GH-binding protein (GHBP). Addi tionally, these mRNAs are alternatively spliced in the 5'-untranslated region, resulting in at least two classes of GHR and GHBP mRNA with distinct first exons and identical coding regions. These alternative first exons define two unique classes of GHR and GHBP mRNA (called GHR(1) and GHR(2)). The GHR(1) class of RNA is expressed only in the liver, is far more abundant in females than males, and is particularly abundant during pregnancy. GHR(1) RNA is induced later in development than is GHR(2). Additional classes of GHR and GHBP RNA may also exist. The genomic structure of the GHR(1) first exon reveals a putative promotor region with no TATA box, CAAT box, or other sequence elements suggesting specific responses. An in vivo approach was used to investigate the regulation of GHR(1) expression. In female rats, gonadectomy was found to reduce the percentage of steady state GHR(1) RNA levels in the liver, whereas male castration resulted in an induction of GHR(1) RNA. However, short-term treatment with estrogen or testosterone had little effect, suggesting that direct regulation of GHR(1) expression may occur through effector(s) other than gonadal steroids. Hypophysectomy abolished GHR(1) RNA in females. Treatment of hypophysectomized females and castrated males with GH by single injection did not significantly induce GHR(1) RNA, but treatment by continuous infusion of GH did. Little change in non-GHR(1) RNA levels was observed for each of these treatments. The results suggest that: 1) the sexual dimorphism observed in total GHR and GHBP RNA in rat liver is attributable to the sexually dimorphic expression of the GHR(1) class of RNA; 2) the sexually dimorphic pattern of GH release in rats regulates the GHR, class of RNA; 3) changes in GHR and GHBP expression observed on gonadectomy, hypophysectomy, GH treatment, and pregnancy are best attributed to GHR(1) regulation; and 4) since GHR(1) is liver specific, the observed increases in serum GHBP concentration in response to sex steroids, GH pattern, and pregnancy are likely to originate from the liver.