Prolactin mediates its effect on target cells through an interaction with membrane-anchored receptors. In the last decade, several subtypes of the receptor have been isolated from different species. This has generated a great deal of interest in the roles of the receptor subtypes and the possible divergent signalling pathways in mediating the pleiotropic effects of prolactin on target tissues. Our current knowledge of the signalling pathway of prolactin is derived mainly from the interaction of the hormone with one of its receptor subtypes (the long form) isolated from rats. In vitro expression studies have led to the identification of the regions within the long form prolactin receptor that are essential for the association of the tyrosine kinase Jak-2, and the phosphorylation events leading to activation of the prolactin responsive beta-casein promoter. To date, a specific target gene that may be activated after interaction of prolactin with the short form of the receptor has not been identified. However, the different receptor subtypes are present in the same cell type in vivo and their expression is hormone regulated, possibly through multiple promoters that control transcription of the prolactin receptor gene. Comparative studies suggest that the signalling pathways and the relevance of different receptor subtypes on prolactin function may vary between species.
HN Jabbour and PA Kelly
HN Jabbour and HO Critchley
Successful establishment of pregnancy is dependent on uterine receptivity at the time of trophoblast invasion and implantation. The endometrium undergoes morphological and functional differentiation during the mid- to late secretory phase of the menstrual cycle in preparation for such an event. These changes are orchestrated by ovarian steroid hormones. However, local autocrine-paracrine signalling at the deciduo-placental interface is crucial for successful establishment of pregnancy. One key cytokine that may regulate many functions in implantation is prolactin. Prolactin is secreted by the decidualized endometrium at the time of predicted conception and, in the event of pregnancy, local expression and secretion of prolactin persists until term. Prolactin mediates its effect on target cells through interaction with single-pass transmembrane receptors. Localization of the sites of expression of the prolactin receptor indicates that the cytokine may regulate an array of functions in the pregnant uterus that are crucial in im-plantation and early pregnancy.
KJ Sales and HN Jabbour
Prostaglandins are bioactive lipids produced from arachidonic acid by cyclooxygenase (COX) enzymes and specific terminal prostanoid synthase enzymes. After biosynthesis, prostaglandins exert an autocrine-paracrine function by coupling to specific prostanoid G protein-coupled receptors to activate intracellular signalling and gene transcription. For many years, prostaglandins have been recognized as key molecules in reproductive biology by regulating ovulation, endometrial physiology and proliferation of endometrial glands and menstruation. More recently, a role for COX enzymes and prostaglandins has been ascertained in reproductive tract pathology, including carcinomas, menorrhagia, dysmenorrhoea and endometriosis. Although the mechanism by which prostaglandins modulate these pathologies is still unclear, a large body of evidence supports a role for COX enzymes, prostaglandins and prostaglandin receptor signalling pathways in angiogenesis, apoptosis and proliferation, tissue invasion and metastases and immunosuppression. Here, an overview is provided of some of the findings from these studies with specific emphasis on the role of COX enzymes, prostaglandin E(2) and F(2alpha) in disorders of endometrial proliferation and menstruation in non-pregnant women.
KJ Demmers, HN Jabbour, DW Deakin and AP Flint
The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.