TY - JOUR
T1 - Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells
AU - Møldrup, Annette
AU - Petersen, Elisabeth D.
AU - Nielsen, Jens Høiriis
PY - 1993/9
Y1 - 1993/9
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Newborn
KW - Female
KW - Gene Expression
KW - Gonadal Steroid Hormones
KW - Growth Hormone
KW - Insulinoma
KW - Islets of Langerhans
KW - Kinetics
KW - Lactation
KW - Male
KW - Pancreatic Neoplasms
KW - Placental Lactogen
KW - Pregnancy
KW - Pregnancy Proteins
KW - Prolactin
KW - RNA, Messenger
KW - Rats
KW - Rats, Wistar
KW - Receptors, Prolactin
KW - Receptors, Somatotropin
KW - Tumor Cells, Cultured
M3 - Journal article
C2 - 8365359
SN - 0013-7227
VL - 133
SP - 1165
EP - 1172
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -