Advances in science and applications of air pollution monitoring: A case study on oil sands monitoring targeting ecosystem protection.

The potential environmental impact of air pollutants emitted from the oil sands industry in Alberta, Canada, has received considerable attention. The mining and processing of bitumen to produce synthetic crude oil, and the waste products associated with this activity, lead to significant emissions of gaseous and particle air pollutants. Deposition of pollutants occurs locally (i.e., near the sources) and also potentially at distances downwind, depending upon each pollutant's chemical and physical properties and meteorological conditions. The Joint Oil Sands Monitoring Program (JOSM) was initiated in 2012 by the Government of Canada and the Province of Alberta to enhance or improve monitoring of pollutants and their potential impacts. In support of JOSM, Environment and Climate Change Canada (ECCC) undertook a significant research effort via three components: the Air, Water, and Wildlife components, which were implemented to better estimate baseline conditions related to levels of pollutants in the air and water, amounts of deposition, and exposures experienced by the biota. The criteria air contaminants (e.g., nitrogen oxides [NOx], sulfur dioxide [SO2], volatile organic compounds [VOCs], particulate matter with an aerodynamic diameter <2.5 µm [PM2.5]) and their secondary atmospheric products were of interest, as well as toxic compounds, particularly polycyclic aromatic compounds (PACs), trace metals, and mercury (Hg). This critical review discusses the challenges of assessing ecosystem impacts and summarizes the major results of these efforts through approximately 2018. Focus is on the emissions to the air and the findings from the Air Component of the ECCC research and linkages to observations of contaminant levels in the surface waters in the region, in aquatic species, as well as in terrestrial and avian species. The existing evidence of impact on these species is briefly discussed, as is the potential for some of them to serve as sentinel species for the ongoing monitoring needed to better understand potential effects, their potential causes, and to detect future changes. Quantification of the atmospheric emissions of multiple pollutants needs to be improved, as does an understanding of the processes influencing fugitive emissions and local and regional deposition patterns. The influence of multiple stressors on biota exposure and response, from natural bitumen and forest fires to climate change, complicates the current ability to attribute effects to air emissions from the industry. However, there is growing evidence of the impact of current levels of PACs on some species, pointing to the need to improve the ability to predict PAC exposures and the key emission source involved. Although this critical review attempts to integrate some of the findings across the components, in terms of ECCC activities, increased coordination or integration of air, water, and wildlife research would enhance deeper scientific understanding. Improved understanding is needed in order to guide the development of long-term monitoring strategies that could most efficiently inform a future adaptive management approach to oil sands environmental monitoring and prevention of impacts. Implications: Quantification of atmospheric emissions for multiple pollutants needs to be improved, and reporting mechanisms and standards could be adapted to facilitate such improvements, including periodic validation, particularly where uncertainties are the largest. Understanding of baseline conditions in the air, water and biota has improved significantly; ongoing enhanced monitoring, building on this progress, will help improve ecosystem protection measures in the oil sands region. Sentinel species have been identified that could be used to identify and characterize potential impacts of wildlife exposure, both locally and regionally. Polycyclic aromatic compounds are identified as having an impact on aquatic and terrestrial wildlife at current concentration levels although the significance of these impacts and attribution to emissions from oil sands development requires further assessment. Given the improvement in high resolution air quality prediction models, these should be a valuable tool to future environmental assessments and cumulative environment impact assessments.

Obestatin and adropin in Prader-Willi syndrome and nonsyndromic obesity: Associations with weight, BMI-z, and HOMA-IR.

The roles of obestatin and adropin in paediatric obesity are poorly understood. We compared obestatin and adropin concentrations in younger (n = 21) and older children (n = 14) with Prader-Willi syndrome (PWS) and age and BMI-z-matched controls (n = 31). Fasting plasma obestatin and adropin were higher in younger children with PWS than controls; adropin was also higher in older children with PWS. Growth hormone treatment had no effects on obestatin or adropin in PWS. The ratio of ghrelin to obestatin declined from early to late childhood but was higher in older PWS than older controls. Adropin correlated with fasting glucose in the PWS group only. Changes in the ratio of ghrelin to obestatin may suggest changes in the processing of preproghrelin to ghrelin and obestatin during development and differential processing of preproghrelin in PWS.

Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice.

BACKGROUND: Treatment with estrogen in early menopausal women protects against development of hepatic steatosis and nonalcoholic fatty liver disease but estrogen has undesirable side effects, which negate its beneficial effects in premenopausal and postmenopausal women. Targeted therapies require better understanding of the target sites and mechanisms by which estrogen signaling exerts its protective effects in women. Estrogen receptor α (ERα) is thought to be the primary mediator for estrogen signaling to protect against hepatic steatosis. ERα has several mechanisms for signal transduction: (1) inducing gene transcription by direct binding to specific DNA sequences, (2) inducing tethered transcription with other DNA-binding factors, and (3) stimulating nongenomic action through membrane-associated ERα. However, it is still unclear which mechanisms mediate ERα-dependent protection against hepatic steatosis. METHODS: To understand the mechanisms of estrogen signaling for protection against hepatic steatosis in females, we analyzed the global ERα knockout mouse (αERKO), ERα DNA-binding domain mutant mouse (KIKO) and liver-specific ERα knockout mouse (LERKO) fed high-fat diets (HFD). The KIKO mouse disrupts the direct DNA-binding transcription activity but retains tethered transcription regulation and nongenomic action. Hepatic steatosis was evaluated by scoring the macrovesicular and microvesicular steatosis as well as serum alanine aminotransferase (ALT) levels. We analyzed serum testosterone to assess its correlation with hepatic steatosis. RESULTS: Liver fat accumulation was far greater in HFD-fed αERKO and KIKO females than in HFD-fed wild-type (WT) controls. Conversely, HFD-fed LERKO females did not accumulate excess liver fat. HFD-fed αERKO and KIKO females showed higher microvesicular steatosis and ALT levels than WT controls that correlated with increased serum testosterone levels. CONCLUSIONS: ERα-mediated direct transcription in non-hepatic tissues is essential for estrogen-mediated protection against hepatic steatosis in HFD-fed females. The balance between non-hepatic estrogen signaling and hepatic or non-hepatic testosterone action may control hepatic steatosis.

Autonomic nervous system dysfunction in obesity and Prader-Willi syndrome: current evidence and implications for future obesity therapies.

The autonomic nervous system (ANS) controls essential functions like breathing, heart rate, digestion, body temperature and hormone levels. Evidence suggests that ANS dysfunction is associated with adult and childhood obesity and plays a role in the distribution of total body fat and the development of obesity-related complications in humans. This review summarizes our current understanding of ANS involvement in the pathogenesis of obesity and Prader-Willi syndrome. Available evidence of ANS dysfunction in the control of energy balance is limited and, in some cases, contradictory. Further investigation in this area is warranted in order to better understand the important contributions of the ANS to regulation of body fat, development of obesity and its comorbidities. Results from these studies will guide the development of novel obesity therapeutics targeting specific ANS dysfunction.

Regulation of maternal metabolism by pituitary and placental hormones: roles in fetal development and metabolic programming.

This review outlines the regulation of maternal metabolism by hormones, cytokines and growth factors, highlighting recent studies that implicate disordered somatolactogen signalling in the pathogenesis of perinatal growth failure and the development of the metabolic syndrome.

Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5.

GH and PRL stimulate insulin production in pancreatic beta-cells through induction of insulin gene transcription. The transcriptional effects of GH are mediated through the binding of signal transducer and activator of transcription-5 (STAT5) to a consensus recognition sequence (TTCnnnGAA) in the rat insulin-1 promoter. In this study we demonstrate that PRL also induces the binding of STAT5 proteins to the rat insulin-1 STAT5 motif. However, the magnitude of binding of STAT5 nuclear proteins, as assessed by electrophoretic mobility shift assays, was only 1/30th that of the binding of the same STAT5 proteins to the beta-casein STAT5 site. The differences in the affinities of the rat insulin-1 and beta-casein STAT5 motifs are explained in part by differences in promoter sequences flanking the STAT5 sites. To assess the importance of the STAT motif in PRL induction of insulin gene transcription, we deleted the STAT5 consensus sequence in the rat insulin 1 promoter, cloned the truncated promoter upstream of the luciferase reporter gene, and transfected the construct into rat insulinoma (INS-1) cells. The transcriptional activity of this construct was compared with that of the wild-type promoter. Although deletion of the STAT5 site in the promoter reduced the basal luciferase activity, the response to PRL was unaffected. PRL also induced transcription of constructs containing the wild-type human insulin promoter or the rat insulin-2 promoter, which contain no classic STAT5 sequences. The transcriptional effect of PRL was manifest even when cells were incubated in glucose-free medium, indicating that the action of the hormone is not mediated solely through changes in glucose uptake or glucose metabolism. To identify PRL-responsive regions of the rat and human insulin promoters, we constructed a series of promoter truncations and assessed their responsiveness to PRL. A PRL-responsive region of the rat insulin-1 promoter was localized between nucleotides -165 and -109. A PRL-responsive region of the human insulin promoter was localized between nucleotides -346 and -250. Additional regions of the human and rat insulin-1 promoters were required for PRL induction of a heterologous, minimal thymidine kinase promoter, suggesting that there are multiple PRL-responsive elements in the insulin genes. These observations suggest a glucose- and STAT5-independent pathway by which PRL may induce insulin gene transcription.

Ontogenesis of prolactin receptors in the human fetus: roles in fetal development.

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 is detected first in exocrine tissue and ductal epithelium. Later in gestation and in the postnatal period, PRLRs predominate in pancreatic beta-cells. The lactogens regulate beta-cell proliferation and insulin production in pancreatic islets, and the insulin secretory response to glucose is blunted in PRLR-deficient mice. These observations suggest roles for the lactogens in pancreatic development and function during pregnancy and postnatal life.

Prolactin receptor signal transduction pathways and actions determined in prolactin receptor knockout mice.

Prolactin-receptor-deficient mice are a good model in which to study the various actions of prolactin. Female homozygous knockout mice are completely infertile and show a lack of mammary development, while hemizogotes are unable to lactate following their first pregnancy. Male and female homozygotes have markedly elevated serum prolactin levels, and in some instances pituitary hyperplasia is present. Maternal behaviour is severely affected in both hemizygous and homozygous animals. Bone formation is reduced in young animals and in adults (males and females). Finally, older males and females show a slight reduction in body weight, which seems to be due to reduced abdominal fat deposition in the knockout animals.

The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.

OBJECTIVES: The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation. Although the factors that contribute to the development of type 2 diabetes are complex and not wholly elucidated, the triad of severe obesity, hyperinsulinemia, and a family history of type 2 diabetes places a child at an increased risk for development of the disease. Current approaches to the prevention of type 2 diabetes, including dietary counseling and exercise, have had limited success. We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients. To that end, we conducted a double-blind, placebo-controlled study of the effects of metformin on body mass index (BMI), serum leptin, glucose tolerance, and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. METHODS: The study population consisted of 29 white and black adolescents aged 12 to 19 years. All had BMIs exceeding 30 kg/m(2). Criteria for enrollment included: 1) a fasting insulin concentration exceeding 15 microU/mL; and 2) at least 1 first- or second-degree relative with type 2 diabetes. All patients had fasting plasma glucose concentrations <110 mg% and hemoglobin A1c concentrations

Body weight and fat deposition in prolactin receptor-deficient mice.

To explore the roles of the lactogens in adipose tissue development and function, we measured body weight, abdominal fat content, and plasma leptin concentrations in a unique model of lactogen resistance: the PRL receptor (PRLR)-deficient mouse. The absence of PRLRs in knockout mice was accompanied by a small (5-12%), but progressive, reduction in body weight after 16 weeks of age. Females were affected to a greater degree than males. The reduction in weight in female PRLR-deficient mice (age 8-9 months) was associated with a 49% reduction in total abdominal fat mass and a 29% reduction in fat mass expressed as a percentage of body weight. Lesser reductions were noted in male mice. Plasma leptin concentrations were reduced in females but not in males. That the reductions in abdominal fat may reflect in part the absence of lactogen action in the adipocyte is suggested by the demonstration of PRLR messenger RNA in normal mouse white adipose tissue. Nevertheless, steady state levels of PRLR messenger RNA in mature adipocytes are very low, suggesting that the effects of lactogens might be mediated by other hormones or cellular growth factors. Our observations suggest roles for the lactogens in adipose tissue growth and metabolism in pregnancy and postnatal life.

The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development.

The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary GH (hGH-N) expression in the mother is suppressed; and hGH-V, a GH variant expressed by the placenta, becomes the predominant GH in the mother. hPL, which is the product of the hPL-A and hPL-B genes, is secreted into both the maternal and fetal circulations after the sixth week of pregnancy. hGH-V and hPL act in concert in the mother to stimulate insulin-like growth factor (IGF) production and modulate intermediary metabolism, resulting in an increase in the availability of glucose and amino acids to the fetus. In the fetus, hPL acts via lactogenic receptors and possibly a unique PL receptor to modulate embryonic development, regulate intermediary metabolism and stimulate the production of IGFs, insulin, adrenocortical hormones and pulmonary surfactant. hGH-N, which is expressed by the fetal pituitary, has little or no physiological actions in the fetus until late in pregnancy due to the lack of functional GH receptors on fetal tissues. hGH-V, which is also a potent somatogenic hormone, is not released into the fetus. Taken together, studies of the hGH/hPL gene family during pregnancy reveal a complex interaction of the hormones with one another and with other growth factors. Additional investigations are necessary to clarify the relative roles of the family members in the regulation of fetal growth and development and the factors that modulate the expression of the genes.

Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.

Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently stimulates beta-cell replication and insulin production, it is unclear whether the effects of prolactin (PRL) on insulin gene expression are exerted directly or through the uptake and/or metabolism of glucose. We examined the interactions between glucose and PRL in the regulation of insulin gene transcription and the expression of glucose transporter-2 (glut-2) and glucokinase mRNAs in rat insulinoma (INS-1) cells. In the presence of 5.5 mM glucose, the levels of preproinsulin and glut-2 mRNAs in PRL-treated cells exceeded the levels in control cells (1.7-fold, P<0.05 and 2-fold, P<0.05 respectively). The maximal effects of PRL were noted at 24-48 h of incubation. PRL had no effect on the levels of glucokinase mRNA. The higher levels of glut-2 mRNA were accompanied by an increase in the number of cellular glucose transporters, as demonstrated by a 1. 4- to 2.4-fold increase in the uptake of 2-deoxy-d-[(3)H]glucose in PRL-treated INS-1 cells (P<0.001). These findings suggested that the insulinotropic effect of PRL is mediated, in part, by induction of glucose transport and/or glucose metabolism. Nevertheless, even in the absence of glucose, PRL stimulated increases in the levels of preproinsulin mRNA (3.4-fold higher than controls, P<0.0001) and glut-2 mRNA (2-fold higher than controls, P<0.01). These observations suggested that PRL exerts glucose-independent as well as glucose-dependent effects on insulin gene expression. Support for this hypothesis was provided by studies of insulin gene transcription using INS-1 cells transfected with a plasmid containing the rat insulin 1 promoter linked to a luciferase reporter gene. Glucose and PRL, alone and in combination, stimulated increases in cellular luciferase activity. The relative potencies of glucose (5.5 mM) alone, PRL alone, and glucose plus PRL in combination were 2.2 (P<0.001), 3.4 (P<0.01), and 7.9 (P<0.0001) respectively. Our findings suggest that glucose and PRL act synergistically to induce insulin gene transcription.

Constitutive expression of placental lactogen in pancreatic beta cells: effects on cell morphology, growth, and gene expression.

To explore the roles of lactogens in islet function, we generated a stable line of rat insulinoma (INS-1) cells that express rat placental lactogen II (rPLII) constitutively in culture. We used this cell line (Ins-rPLII) to examine the effects of endogenous rPLII on beta-cell growth, islet formation, and the expression of glucose transporter 2 (glut-2) and insulin mRNA. Growth and maturation of Ins-rPLII cells were compared with that of cells transfected stably with an empty expression plasmid (control) and of INS-1 cells treated with exogenous prolactin. The Ins-rPLII cells proliferated more rapidly than control cells in serumfree medium and showed distinct morphologic characteristics in culture. Whereas the control cells flattened readily on plastic and formed a branching monolayer, the Ins-rPLII cells remained more rounded, sent out fewer projections, and formed more numerous (p<0.01) and larger (p<0.01) beta-cell clusters. Larger clusters assumed a spherical form with well-delineated smooth borders and detached more readily from the culture plates. Maturational progression of the Ins-rPLII cells was associated with a 40% increase in preproinsulin mRNA (p<0.05) and a 2-3-fold increase in glut-2 mRNA (p<0.01). Induction of glut-2 mRNA was accompanied by a 1.4-2.4-fold increase (p< 0.01) in the uptake of radiolabeled 2-deoxyglucose. Similar effects were observed in INS-1 cells exposed for 48 h to exogenous prolactin. These findings suggest novel roles for the lactogenic hormones in the maturation and growth of pancreatic islets. Lactogen induction of beta-cell aggregation coupled with localized beta-cell growth may contribute to the expansion of islet mass that occurs in pregnancy and during the perinatal period. The induction of insulin and glut-2 mRNA provides a mechanism by which the lactogens may increase fetal and maternal insulin production and enhance the sensitivity of the pancreas to glucose.

Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development.

To explore potential roles for lactogenic hormones in human fetal development, we examined the distribution and ontogenesis of expression of prolactin receptors (PRLRs) in human fetal tissues at 7.5-14 wk of gestation and in tissues of the embryonic and fetal rat on days e12.5-e20.5. Histochemical analysis of PRLR immunoreactivity in the human fetus and fetal rat revealed novel and unexpected patterns of receptor expression. Most remarkable was the appearance in early fetal development of intense PRLR immunoreactivity in tissues derived from embryonic mesoderm, including the periadrenal and perinephric mesenchyme, the pulmonary and duodenal mesenchyme, the cardiac and skeletal myocytes, and the mesenchymal precartilage and maturing chondrocytes of the endochondral craniofacial and long bones, vertebrae and ribs. Striking changes in the cellular distribution and magnitude of expression of PRLRs were noted in many tissues during development. In the fetal adrenal the initial mesenchymal PRLR expression is succeeded by the emergence of PRLR immunoreactivity in deeper fetal cortical cell layers. In the fetal kidney and lung, the invagination of cortical mesenchyme is accompanied by progressive PRLR immunoreactivity in bronchial and renal tubular epithelial cells. In the pancreas, the PRLR is expressed primarily in acinar cells and ducts in early gestation; in late gestation and in the postnatal period, the PRLR is expressed predominantly in pancreatic islets, co-localizing with insulin and glucagon. Finally in fetal hepatocytes, PRLR immunoreactivity increases significantly between embryonic days e52 and e96 in the human fetus and between days e16.5 and e18.5 in the fetal rat. In addition to playing important roles in reproduction, lactation, and immune function, the lactogenic hormones likely play roles in tissue differentiation and organ development early in gestation.

Ontogenesis of prolactin receptor gene expression in the rat olfactory system: potential roles for lactogenic hormones in olfactory development.

The PRL receptor (PRLR) is expressed at very low levels in the olfactory bulb of the adult rat but is detected in abundance in the olfactory epithelium and olfactory bulb of the fetal rat in late gestation. To explore potential roles for the lactogenic hormones in olfactory differentiation and development, we have used in situ hybridization and immunohistochemistry to examine the ontogeny of PRLR gene expression in the rat olfactory system. At midgestation (embryonic day 12.5), messenger RNAs (mRNAs) encoding the long and short isoforms of the rat PRLR were detected in the medial and lateral nasal processes, the epithelial lining of the olfactory pit, and the neuroepithelium lining the cerebral ventricles in the region of the rhinencephalon. PRLR mRNA was also expressed prominently in the frontonasal mesenchyme and in mesenchymal tissue underlying the developing brain and overlying the pontine flexure in the interpeduncular fossa. The distribution of PRLR immunoreactivity was similar to that of PRLR mRNA, indicating that the PRLR gene is translated to that of PRLR mRNA, indicating that the PRLR gene is translated to lactogenic binding protein in the rat embryo in vivo. With advancing gestation, the PRLR was expressed intensely, although discontinuously, in the olfactory epithelium and was detected in the cartilage primordia of the ethmoid, sphenoid, temporal, and mandibular bones. PRLR expression in the vomeronasal organ was confined to the luminal epithelial surface. PRLR mRNA and immunoreactive protein were first detected in the olfactory bulb on embryonic day 18. PRLR expression was most intense initially in the periventricular neuroepithelium; subsequently, robust staining of the mitral and tufted cell neurons became apparent, accompanied by intense PRLR expression in the sensory neuronal cell bodies of the olfactory epithelium. By postnatal day 5, the PRLR was expressed in abundance in mitral and tufted cells of the olfactory bulb and in neuronal cell bodies of the anterior olfactory nucleus and the piriform cortex. PRLR mRNA was also detected in the mitral cells of the olfactory bulb of the lactating rat, although at levels far lower than those in the fetal or neonatal rat. The expression of the PRLR in the olfactory system of the fetal and neonatal rat implicates novel roles for the lactogenic hormones in olfactory differentiation and development and may provide new mechanisms by which the lactogens may regulate neonatal behavior and maternal-infant interactions.

The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation.

The cellular distribution and developmental expression of the PRL receptor (PRLR) in the late gestational fetal rat were examined by in situ hybridization, immunohistochemistry, and radioligand binding. Antisense and sense strand RNA probes encoding the long and short isoforms of the rat PRLR were hybridized to tissue sections under stringent conditions. Messenger RNA (mRNA) encoding the two isoforms of the receptor was expressed widely in tissues derived from all three germ layers; these included various tissues not known previously to contain lactogenic receptors, such as the olfactory neuronal epithelium and olfactory bulb, trigeminal and dorsal root ganglia, cochlear duct, brown adipose tissue, submandibular glands, whisker follicles, tooth primordia, and proliferative and maturing chondrocytes of developing bones. Prominent expression of PRLR mRNA was also detected in the fetal adrenal cortex, gastrointestinal and bronchial mucosae, renal tubular epithelia, choroid plexus, thymus, liver, pancreas, and epidermis. Immunohistochemical studies using monoclonal anti-PRLR antibodies demonstrated that the distribution of PRLR immunoreactivity was similar to that of PRLR mRNA, suggesting that the PRLR mRNA is translated to receptor protein in the fetus in vivo. The encoding of functional PRL receptor proteins by fetal PRLR mRNA was revealed by the presence of specific rat placental lactogen II-binding sites in fetal adrenal cortex, renal tubules, small intestinal villi, pancreatic ductules and islets, hepatic parenchymal cells, choroid plexus ependymal cells, and microsomal fractions of fetal lung and thymus. Levels of expression of PRLR mRNA and protein increased between days 17.5 and 20.5 of gestation in a number of fetal tissues, including the adrenal, pancreas, small intestine, pituitary, thymus, liver, and submandibular gland. The widespread expression of the PRLR in the fetal rat and the induction of receptor expression in late gestation suggest novel roles for the lactogenic hormones in fetal and neonatal development.

Human placental lactogen infusions into the medial preoptic area stimulate maternal behavior in steroid-primed, nulliparous female rats.

The effects of central administration of human placental lactogen (hPL) on the onset of maternal behavior were measured in steroid-primed, adult ovariectomized, nulliparous rats. Rats were fitted with bilateral cannulas directed at the medial preoptic area (MPOA) and gonadectomized 1 week before being implanted sc with progesterone (P)-filled Silastic implants (treatment Day 1). On Day 11 P capsules were removed, and each female was implanted sc with a single estradiol (E2) capsule. On Days 11 to 13 animals were infused bilaterally with 40 ng of hPL/infusion or given 0.4 microliter vehicle. Subjects were given hormone or vehicle infusions five times during this period, twice each on Days 11 and 12 (1000 and 1600 hr) and once on Day 13 (1000 hr). Behavioral testing began on day 12 after the 1000 hr infusions and continued daily for 6 days. All females were injected sc twice daily with bromocriptine (2 mg/ke) to suppress endogenous PRL secretion from Day 11 to the completion of testing. The results showed that central infusions of hPL stimulated a fast onset of maternal behavior relative to controls. Latencies to display specific components as well as complete maternal behavior toward foster young were about 1 day in the hPL-treated group and 4 days in vehicle-infused controls. Infusions of hPL into the MPOA between 7.8 and 8.0 AP resulted in the fastest rate of onset of maternal behavior. These findings demonstrate that central infusion of a heterologous placental lactogen, hPL, is capable of stimulating maternal behavior may normally be brought about by exposure to placental lactogens as well as prolactin.