During pregnancy, marked
hyperplasia of the pancreatic islet cells has been observed. This effect may be mediated by the pregnancy-associated
peptide hormones,
placental lactogen, PRL, and GH, which were previously shown to be mitogenic to beta-cells in vitro. To study whether the responsiveness of islet cells to these
hormones is regulated on the receptor level, GH and PRL receptor gene expression was studied in pancreata from male rats and virgin, pregnant, and lactating female rats and in cultured islets and
insulinoma cells (RIN-5AH) in response to various
hormones. The
mRNA levels were quantitated by
ribonuclease protection assay, using probes specific for
mRNA encoding, extracellular and intracellular domains of the GH receptor, and short and long forms of the PRL receptor, respectively. Specific transcripts for the GH receptor were present in pancreas, islets, and RIN-5AH cells. Furthermore, as previously observed in RIN-5AH cells, a predominant expression of the long form of PRL receptor vs. the short form was also found in pancreas and islet cells. Male and nonpregnant female pancreas did not differ significantly in their levels of GH and PRL receptor mRNAs. On day 14 of pregnancy, increases in both GH and PRL receptor
mRNA levels were observed (1.7- and 2.4-fold, respectively), and a further increase occurred in late pregnancy (day 19), when GH and PRL receptor
mRNA levels were 2.7- and 3.9-fold higher than those in the nonpregnant state.
mRNA levels returned toward the basal level during lactation. In the cultured islets, PRL receptor
mRNA levels were markedly increased by GH and PRL (3.5- and 6.5-fold, respectively) after exposure for 24 h, whereas
estradiol and
testosterone had modest stimulating effects (1.8- and 1.5-fold increases, respectively).
Dexamethasone induced a 2.5-fold increase in GH receptor
mRNA levels, and a weak stimulatory effect was also observed for
progesterone. In RIN-5AH cells, the effect of
dexamethasone on GH receptor
mRNA was detectable after 2 h and maximal after 16 h. In contrast, the effects of GH and PRL on PRL receptor
mRNA required 24-48 h of exposure. The effective doses were within the physiological ranges. In conclusion, these results show a differential hormonal regulation of GH and PRL receptor gene expression in the pancreatic islets, which may play a role in the adaptive beta-cell growth during pregnancy.