Effects of deletion of the prolactin receptor on ovarian gene expression

Abstract

Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.

Differential hypermethylation of SOCS genes in ovarian and breast carcinomas

“…SOCS proteins have been demonstrated to act as potent inhibitors of Prl signaling in different cellular systems in vitro (Helman et al, 1998;Pezet et al, 1999;Tomic et al, 1999;Lindeman et al, 2001) and we have established a physiological role for SOCS1 as a negative regulator of the prolactin pathway in the mammary gland (Lindeman et al, 2001). Targeted deletion of Prl and its receptor (PrlR) has revealed that these genes play an essential role in mammary and ovarian development and in the maintenance of pregnancy (Horseman et al, 1997;Ormandy et al, 1997;Grosdemouge et al, 2003). Other cytokines, including growth hormone and IL-6, which are also regulated by SOCS proteins, appear to exert key functions in these organs.…”

Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/β-catenin synergy

“…All transfections were performed in triplicate and normalized with ␤-galactosidase activity (carried by pCMV-␤Gal, 0.1 g) for transfection efficiency. TRIzol reagent (GIBCO͞BRL) was used to extract total RNA from coculture cells; primers and RT-PCR conditions were as described (2,22,23).…”

The Short Prolactin Receptor Predominates in Endothelial Cells of Micro- and Macrovascular Origin

“…It is likely be involved in angiogenesis, e.g. of the ovary [15, 16] and testis [29]. Studies by other investigators [7, 8, 30] and our own group (unpubl.…”

“…The expression of the two PRL-R forms varies in the CL depending on the oestrous cycle, on pregnancy and lactation [14]. CL-derived EC appear to be sensitive to PRL, because Gaytan et al [15] observed a higher proliferative activity of EC in the CL of pregnant rats than of cycling rats; even more supporting, Grosdemouge et al [16] reported on extensive inhibition of angiogenesis during CL development in mice with targeted disruption of the PRL-R gene. For these reasons, microvascular EC from the CL appear particularly promising for the study of PRL-R forms with angiogenic potentials, even more as endocrine gland-derived EC are found to be unique in their response to certain growth factors, e.g.…”

“…This luteotrophic effect certainly plays a role in the non-rodent [50] and rodent system [15]. PRL-R-deficient mice suffer from an insufficient vascular bed accompanied by an inferior CL function [16]. …”