Female Reproductive Tract

Differences in Prolactin Receptor (PRLR) in Mouse and Human Fallopian Tubes: Evidence for Multiple Regulatory Mechanisms Controlling PRLR Isoform Expression in Mice

Abstract
The anterior pituitary-derived hormone prolactin signals through the prolactin receptor (PRLR) and it is important for female reproductive function in mammals. In contrast to the extensive studies of PRLR expression and regulation in human and mouse ovary and uterus, the mechanisms controlling the regulation of PRLR isoform expression in the fallopian tube are poorly understood. Since dynamic interaction of hormonal signaling presented in either gonadal tissue and the pituitary or gonadal tissues themselves in mammals suggest endocrine and/or paracrine regulation of PRLR expression, we questioned whether differential regulation of PRLR isoforms by PRL, ovarian-derived estrogen (E₂) and progesterone (P₄) exists in the fallopian tube and pituitary of prepubertal female mice. Western blot analysis showed distinct molecular separation of PRLR isoforms in both mouse and human fallopian tubes and cellular localization was found in both mouse and human tubal epithelia but not mouse tubal smooth muscle cells. These data support the concept of an isoform- and cell type-specific expression of PRLR in human and mouse fallopian tubes. Moreover, expression of the long form of the PRLR decreased after PRL treatment and increased after blockage of endogenous PRL secretion by bromocriptine (an inhibitor of PRL secretion) in a time-dependent manner in mouse fallopian tube. The opposite regulation was observed in the pituitary. Treatment with exogenous E₂ or P₄ led to similar changes in PRLR expression in the fallopian tube as PRL treatment. E₂ and P₄ did, however, not affect PRLR expression in the pituitary. Interestingly, E₂ had no effect on the long form of PRLR expression, whereas P₄, as PRL, regulated the long form of PRLR in the fallopian tube. Taken together, our comparative study provides evidences that PRLR can be regulated by an interplay of two different mechanisms, either PRL or ovarian steroid hormones independently, or in combination in a tissue-specific manner. Furthermore, we found that ovarian steroid hormones selectively suppress the expression of PRLR isoforms in mouse fallopian tubes. These findings may contribute to our understanding of the mechanisms controlling PRLR isoform expression in the fallopian tube, in addition to ovary and uterus, with implications for female reproduction.

Key words: Pituitary • Estradiol • Oviduct • Prolactin • Prolactin receptor