CHANGES IN ENDOGENOUS GROWTH-HORMONE SECRETION AND ONSET OF PUBERTY IN TRANSGENIC RATS EXPRESSING HUMAN GROWTH-HORMONE GENE

A chimeric gene comprising murine whey acidic protein (mWAP) and human growth hormone (hGH) was used to produce transgenic rats that express hGH and secrete it into the blood. Two lines of transgenic rats carry ing the mWAP/hGH construct were established: Line 1 was characterized by relatively high levels of serum hGH, and Line 2 had relatively low levels. The secretory profiles of rat GH (rGH) as well as hGH, the tra nsgene product, were obtained in transgenic males and females of Line 2; both hGH and rGH serum levels were flattened with no episodic fluct uations, and the overall mean concentration of rGH was significantly l ower than in normal littermates. Although the animals of Line 1 showed an accelerated increase in growth rate, those of Line 2 did not. Neve rtheless, the onset of puberty in females, as assessed by vaginal open ing and occurrence of first ovulation, advanced by 7-8 days in both Li nes of animals. Accordingly, the body weight at puberty of Line 2 tran sgenic females was much lower than that of normal littermates, indicat ing that continuous hGH expression could induce precocious puberty wit hout enhancing the growth rate.