Transgenic Mice Harboring Murine Luteinizing Hormone Receptor Promoter/β-Galactosidase Fusion Genes: Different Structural and Hormonal Requirements of Expression in the Testis, Ovary, and Adrenal Gland

Abstract

AbstractIn vivo regulation of the LH receptor (LHR) promoter was studied using transgenic (TG) mice harboring fusion genes containing three different lengths of the LHR promoter (7.4 kb, 2.1 kb, and 173 bp), fused with coding sequence of the Escherichia coli β-galactosidase (β-GAL) reporter gene. The length of the LHR promoter significantly affected the pattern of β-GAL expression. In the testis the shortest promoter directed expression primarily of the full-length β-GAL mRNA, but mainly truncated messages were transcribed from the longer LHR promoter/β-GAL constructs. The case was reversed in the ovary and adrenal gland. Furthermore, we have recently detected strong LHR expression in the adrenal gland of female mice with chronically elevated serum LH. Therefore, the regulation of the adrenal LHR expression was addressed in the present study using the LHR/β-GAL TG mice. Elevated LH levels were achieved in the LHR/β-GAL mice either by gonadectomy or cross-breeding them with TG mice overexpressing a chimeric protein of bovine LH β-subunit and the C-terminal fragment of human chorionic gonadotropin-β. In both models, β-GAL mRNA was found in the adrenal cortex when the 7.4-kb LHR promoter was applied but not in mice carrying the 173-bp LHR promoter. The 7.4-kb construct was activated also in the ovaries in the double TG LHR(β-GAL)/bovine LH β-subunit/C-terminal fragment of human chorionic gonadotropin-βmice in some theca-interstitial cells surrounding the follicles. Hence, the LHR promoter elements essential for directing β-GAL expression to the adrenal gland and ovary (7.4 kb) are different from those recently shown to be essential for the testicular expression (173 bp). In conclusion, elevated serum LH concentrations were found seminal for the LHR promoter activation in the ovaries and adrenals, and different lengths of the promoter are responsible for reporter gene expression in the testis, ovary, and adrenal gland.