Species-specificity of growth-promoting effects of prolactin during rat embryogenesis (original) (raw)
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Visualisation of the Uptake of Prolactin (PRL) in Rat Embryonic Tissues
Marmara Medical Journal, 1999
Objective: Evidences implicate roles for prolactin (PRL) in the regulation of embryonic growth. To clarify the roles of PRL in rat embryogenesis we examined the uptake and expression of the hormone in embryonic tissues. Methods: Nine and a half day postimplantation rat embryos were cultured in vitro for 44h in rat serum and serum depleted of low molecular weight molecules (retenate). The embryos were transferred to M199 for the last 4h, and 12.8 ng/ml rat PRL was added to culture medium for different times (4h - 15 min) and/or different temperatures (37°C and 4°C). As a control tissue, pituitary glands from 11.5 and 18.5d pregnant rats were used. Embryos and tissues were then examined by an indirect immunofluorescence protocol. Results: The pituitary glands showed positive immunoreactivity for anti-PRL antibody whilst there was no stain in the control brain tissue. Immunoreactivity was observed in embryos grown in rat serum, and intensity was much greater in the presence of addition...
Ontogenesis of prolactin receptors in the human fetus: roles in fetal development
Biochemical Society Transactions, 2001
The lactogenic hormones prolactin (PRL) and placental lactogen circulate in human fetal plasma during mid and late gestation. To explore potential roles for the lactogens in fetal development, we examined the cellular distribution and changes in expression of PRL receptors (PRLRs) during ontogeny, and the metabolic effects of PRL signalling and PRLR dysregulation. PRLRs are expressed in diverse tissues of the human fetus by 7.5 weeks of gestation. In fetal bone, adrenal gland and lung, the receptor is expressed first in mesenchymal cells and subsequently in maturing chondrocytes, adrenocortical cells and bronchiolar epithelial cells. That the lactogens play roles in fetal chondrogenesis is suggested by studies in PRLR-deficient mice, which show a delayed ossification of the calvarium. In the central nervous system, the PRLR is detected initially in periventricular neuroepithelium and later in mature neurons of the hypothalamus and olfactory bulb. Finally, in the pancreas, the PRLR i...
Regulation of Prolactin Release at the End Stage of Chicken Embryogenesis
The Journal of Poultry Science
Difference of onset of increase of PRL content in the anterior pituitary gland and plasma PRL concentration during the late stage of chicken embryogenesis is well known. To investigate the disagreement, changes in PRL content and PRL mRNA levels, and the effects of vasoactive intestinal polypeptides (VIP) on PRL release and PRL mRNA expression were examined using western blot analysis and real-time PCR quantification. Changes in SPRL content were strongly correlated with PRL mRNA levels. The increase in PRL content on day 17 of incubation may be caused by the increase in PRL mRNA levels on day 16 of incubation. Additionally, the effects of VIP on PRL release from the embryonic anterior pituitary gland were not observed until day 18 of embryogenesis. These results suggest that increased levels of PRL mRNA and PRL content in the anterior pituitary gland are closely correlated. However, the increased expression of PRL mRNA observed on day 17 and the initiation of PRL release from the anterior pituitary gland on day 19 were differentially regulated. According to the results of western blot analysis, the proportion of glycosylated PRL (G-PRL) and non-glycosylated PRL (NG-PRL) in the anterior pituitary gland at the end stage of development differed from the proportion of PRL released from the anterior pituitary gland. According to the results of two-dimensional western blot analysis, no isoforms with different isoelectric points were detected in the culture medium on days 19 and 20. These data suggest that the peptide chains of G-PRL and NG-PRL were not modified. In conclusion, the differentiation of PRLproducing cells and the maturation of the hypothalamus and anterior pituitary gland were completed at the end stage of incubation, and that different factors regulated the initiation of PRL mRNA expression before day 18 of incubation.
Journal of Neuroendocrinology, 2001
Prolactin is present in the fetal circulation and prolactin receptors are expressed in a wide range of fetal tissues. The factors which regulate the synthesis and secretion of prolactin, and the expression of its receptors before birth, are poorly understood. We have investigated whether experimental restriction of placental growth in the sheep has an impact on the prolactin axis in the growth restricted fetus. The majority of uterine endometrial caruncles were removed before pregnancy in 10 ewes (placental restriction; PR group). Placental, fetal liver and kidney weights were reduced in the PR compared to the control group (n=10). The ratio of fetal prolactin mRNA : 18S rRNA was signi®cantly lower (P<0.01) in the PR group (1.83t0.45, n=6) than in the control group (4.11t0.54, n=6). The ratio of prolactin mRNA : 18S rRNA in the fetal pituitary was positively correlated with fetal and with placental weight. Using stepwise linear regression, it was determined that the level of fetal prolactin mRNA : 18S rRNA expression was best described (as judged by the maximum adjusted R 2 ) by prolactin mRNA: 18 S rRNA=x3.0378+0.17 PO 2 +2.772 glucose (adjusted R 2 =0.765, F=17.53, P<0.001). Fetal plasma prolactin concentrations were signi®cantly reduced (P<0.05) in the PR group compared to control animals between 109 and 141 days gestation. Fetal prolactin receptor (PRLR) mRNA transcripts encoding long (PRLR1) and short forms (PRLR2) of PRLR were present in the liver and kidney of animals in the PR and control groups at 140±141 days gestation. PR did not alter the levels of PRLR1 or PRLR2 mRNA in the fetal liver or kidney. The suppression of the synthesis and secretion of prolactin in the growth restricted fetus may limit the action of prolactin on the growth and metabolism of key fetal organs during suboptimal intrauterine conditions
Endocrinology, 1997
The corpora lutea of pregnancy in the rat are highly dependent on the action of PRL and PRL-like hormones to hypertrophy and to produce progesterone needed for the maintenance of gestation. Two forms of the PRL receptor (PRL-R), designated as long (PRL-R L ) and short (PRL-R S ), have been described in rat tissues. To determine whether both forms are present in the corpus luteum during pregnancy and to examine the developmental and hormonal regulation of their expression, total RNA isolated from corpora lutea at different stages of pregnancy and from highly luteinized granulosa cells subjected to different hormonal treatments were analyzed by semiquantitative RT-PCR. Immunoblotting of luteal proteins from early and late pregnancy was also performed to determine if the pattern of PRL-R proteins follows that of PRL-R messenger RNA (mRNA) expression. In addition, the correlation between the well characterized PRL-regulated gene, 20␣-hydroxysteroid dehydrogenase (20␣-HSD), and PRL-R gene expression was investigated during the time of luteolysis. Both PRL-R L and PRL-R S mRNA and protein were expressed in corpora lutea of pregnancy, with the long form being the most dominant at all stages. Whereas no changes in mRNA level of either PRL-R L or PRL-R S were found until day 20 of gestation, a profound decline in PRL-R mRNA and protein for both receptor types occurred at the end of pregnancy. This drop in PRL-R expression was accompanied by a sharp and abrupt expression of 20␣-HSD mRNA. Studies performed in vivo and in luteinized cells in culture indicate that PRL can up-regulate the expression of the PRL-R L mRNA, an effect prevented by the tyrosine kinase inhibitor, genistein. PRL-R L mRNA was also selectively increased by cAMP. In summary, the results of this investigation have established that: 1) the corpus luteum of pregnancy expresses both the short and long forms of the PRL-R with the long form being more abundant; 2) the mRNA for both forms of the PRL-R remains at constant levels throughout pregnancy but drops before parturition; 3) the decline in PRL-R mRNA at the end of pregnancy is accompanied by a dramatic rise in 20␣-HSD; 4) PRL is able to increase the expression of PRL-R mRNA; and that 5) both A kinase and tyrosine kinase mediated pathways appear to participate in the up-regulatory mechanism involved in PRL-R mRNA expression. (Endocrinology 138: [4812][4813][4814][4815][4816][4817][4818][4819][4820] 1997)
Endocrinology, 2000
PRL, a hormone secreted essentially by the pituitary and other extrapituitary sources such as decidua, has been attributed regulatory roles in reproduction and cell growth in mammals. These effects are mediated by a membrane PRL receptor belonging to the cytokine receptor superfamily. Null mutation of the PRL receptor gene leads to female sterility due to a severely compromised preimplantation development and a complete failure of the implantation of the few embryos reaching the blastocyst stage, strongly implicating PRL in the maternal control of implantation. We measured the hormonal status of Ϫ/Ϫ mice, which confirmed that the corpus luteum is unable to produce progesterone. Progesterone administration to Ϫ/Ϫ mice completely rescued the development of preimplantatory eggs and embryo implantation. Pregnancy could be maintained to 19.5 days postcoitum, with about 22% of resulting embryos reaching adulthood. Although progesterone and perhaps PRL appear to facilitate mouse preembryo development throughout the preimplantation stages, other factors as well as a possible direct effect of PRL on the uterus are probably necessary to fully maintain pregnancy. Finally, reduced ductal side-branching in the mammary gland can be rescued by progesterone treatment, but females exhibit reduced alveolar formation. Our model establishes the PRL receptor as a key regulator of reproduction and provides novel insights into the function of lactogenic hormones and their receptor.
Cell Proliferation, 1997
Much evidence suggests that prolactin (PRL) has an immunoregulatory function. Part of this evidence is that the receptors for PRL are present on lymphocytes. Probably the effects of PRL on cells of the immune system depend on the level and specific forms of PRL-R present on the target cells. Therefore, PRL-R expression at both protein and mRNA levels was examined during oestrous cycle, pregnancy and lactation using Western blotting and PCR analysis. Antibody to the long form of PRL-R detected 84 and 42 kDa protein bands in the spleen but only 84 kDa band in the thymus. The expression pattern of these two protein bands was different in the spleen, suggesting that these two isoforms of PRL-R long form are differentially regulated by the hormones of oestrous cycle. In addition, depending on the tissue, the level of mRNA for the short and long forms of PRL-R showed a significant change at different stages of oestrous cycle. Moreover, 42 and 84 kDa PRL-R bands were detected in both spleen and thymus throughout the pregnancy and lactation; however, the expression pattern of 84 kDa protein band was different between tissues. This finding suggests that each tissue exhibits differential response to hormones which affect PRL-R content. An anterior pituitary hormone PRL is primarily responsible for the development of mammary gland and the stimulation of milk protein genes. In addition, it has effect on reproduction, growth, metabolism, behaviour and immunoregulation. Immunoregulatory function of PRL has been supported by many studies. For example, decreased antibody production as well as cell mediated immunity have been observed in hypohysectomized rats (Nagy &-Berczi 1978). Administration of PRL or implantation of pituitary gland reconstituted these immune functions (Berczi et al. 1981, Nagy et al. 1983). In addition, PRL has been shown to regulate DNA synthesis in vivo in lymphoid tissue (Berczi et al. 1991) and to act directly on splenocytes and thymocytes in vitro (Mukherjee et al. 1990, Viselli, Stanek & Mukherjee 1991). PRL-R expression has been shown in lymphoid cells. For example, binding studics with '2sI-labelled PRL provided evidence that human T-and B-cells have PRL-R (Russell 1985). More definitive studies based on the use of antibodies to PRL-R and flow cytometry confirmed these findings; and indicated that many subsets of rat splenocytes (Viselli & Mastro 1Y93), rat and murine lymphoid cells (Koh & Phillips 1YY3, Gagnerault et al.