The pituitary hormone prolactin (PRL) is best known for its role in the regulation of lactation. Recent evidence furthermore indicates PRL is required for normal reproduction in rodents. Here, we report on the insertion of two transposon-like DNA sequences in the human prolactin gene, which together function as an alternative promoter directing extrapituitary PRL expression. Indeed, the transposable elements contain transcription factor binding sites that have been shown to mediate PRL transcription in human uterine decidualised endometrial cells and (...) lymphocytes. We hypothesize that the transposon insertion event has resulted in divergent (pituitary versus extrapituitary) expression of prolactin in primates, and in differential actions of pituitary versus extrapituitary prolactin in lactation versus pregnancy respectively. Importantly, the TE insertion might provide a context for some of the conflicting results obtained in studies of PRL function in mice and man. (shrink)

A large number of previous reports described an effect of the pituitary hormone prolactin (PRL) on steroid hormone production by the adrenal cortex. However, those studies remained anecdotal and were never converted into a conceptual and mechanistic framework, let alone being translated into clinical care. In the light of our recently published landmark study where we described PRL signalling as a pivotal regulator of the sexually dimorphic adrenal phenotype in mouse and of adrenal androgen production in humans, we present (...) here the overarching hypothesis that PRL signalling increases the activity of Steroidogenic Factor‐1 (SF‐1/NR5A1), a transcription factor that has an essential role in adrenal gland development and function, to regulate adrenal cortex growth and hormonal production in physiological and pathological conditions. PRL can then be considered as a bona fide adrenocorticotropic hormone synergizing with ACTH in the endocrine control of adrenal cortex function. (shrink)

SummaryCross-sectional studies in Australia and the Philippines and a longitudinal prospective study in a selected Australian sample of breast-feeding mothers have shown that basal serum prolactin concentrations are elevated during 15–21 months of lactational amenorrhoea.A predictive model of serum PRL levels and return of cyclic ovarian activity during full breast-feeding, partial breast-feeding and weaning has been developed from the results of breast-feeding behaviour and serum PRL, gonadotrophin and oestradiol measurements in 34 mothers breast-feeding on demand for a mean of (...) 67 weeks.Breast-feeding patterns influence serum PRL levels. Important factors during full breast-feeding are the age of the baby, the longest interval between feeds at night and total 24-hr suckling time, and following the introduction of supplements, the mean interval between feeds, together with the total 24-hr suckling time and the number of solid supplements per day.The precise mechanisms whereby breast-feeding regulates cyclic ovarian activity remain unknown. Gonadotrophin secretion appears to be quantitatively normal, but qualitative changes, secondary to altered hypothalamic activity, may be the most important factor. A direct inhibitory effect of PRL on ovarian follicular development and steroidogenesis remains possible.Ovulation with a normal luteal phase is probable for 30% of breast-feeding mothers before the first menses, but is unlikely before 6 months, provided breast-feeding is frequent day and night.Measurement of serum PRL is a sensitive index of the return of menstruation and fertility during lactation in the population studied. (shrink)

The present study examines the physiological alterations in prolactin (PRL) messenger ribonucleic acid (mRNA) and serum PRL levels during the rat estrous cycle and the effed of naloxone, an endogenous opioid peptide receptor antagonist, on PRL gene expression during the rat estrous cycle. Adult female rats exhibiting at least two consecutive 4-day estrous cycles were used in this study. A single injection of naloxone (2mg/kg b.w.) or saline was given sc 30 mm prior to decapitation. Animals were sacrificed at (...) 10:00 h of each stage of the estrous cycle, and at 2-h intervals from 10:00 h to 20:00 h during the proestrus. PRL mRNA and serum PRL levels were determined by an RNA-blot hybridization with the rat PRL cDNA probe and by a PRL radioimmunoassay, respectively. PRL mRNA and serum PRL levels were not dramatically altered in the morning of each stage of diestrus I, II, and proestrus, and naloxone failed to modify the two parameters. During estrus naloxone clearly suppressed serum PRL levels, but it was unable to modify PRL mRNA levels. A more detailed examination of the proestrus stage revealed that PRL mRNA and serum PRL levels fluctuated as a function of time: PRL mRNA levels reached a maximum level at 12:00 h and gradually decreased until 18:00 h. PRL mRNA levels then rose at 20:00 h. No difference in PRL mRNA levels between the control and naloxone-treated groups was observed. Changes in serum PRL level during proestrus were conversely related to changes in PRL mRNA: serum PRL levels were low from 10:00 h to 14:00 h, then increased and reached a maximum level at 16:00-18:00 h. Following then, serum PRL levels were decreased. Naloxone was effective in suppressing the characteristic afternoon surge of PRL from 16:00 h to 20:00 h. These data clearly showed that alterations in PRL mRNA levels were conversely correlated with changes in serum PRL levels on proestrus, indicating differential regulation of PRL gene expression and secretion. (shrink)

The molecular evolution of pituitary growth hormone and prolactin in mammals shows two unusual features: episodes of markedly accelerated evolution and, in some species, complex families of related proteins expressed in placenta and resulting from multiple gene duplications. Explanations of these phenomena in terms of physiological adaptations seem unconvincing. Here, I propose an alternative explanation, namely that these evolutionary features reflect the use of the hormones (and their receptors) as viral receptors. Episodes of rapid evolution can then be explained (...) as due to “arms races” in which changes in the hormone lead to reduced interaction with the virus, and subsequent changes in the virus counteract this. Placental paralogues of the hormones could provide decoys that bind viruses, and protect the foetus against infection. The hypothesis implies that the extensive changes introduced into growth hormone, prolactin and their receptors during the course of mammalian evolution reflect viral interactions, not endocrine adaptations. (shrink)

Serum prolactin has been measured in single blood samples collected within the first 22 post-partum months from 97 nursing mothers from an urban area (Bukavu) of Zaïre. Nursing mothers are hyperprolactinemic, higher serum prolactin levels being associated with more frequent suckling episodes per day. Furthermore, serum prolactin declines rapidly in mothers who are giving the breast less than four times per day: the levels are within the normal range found in non-lactating women after the 6th post-partum month. (...) Among mothers giving the breast more than six times per day, serum prolactin does not decline significantly during the 1st post-partum year. (shrink)

Women’s preferences for several male traits, including voices, change over the menstrual cycle, but the proximate causes of these changes are unknown. This paper explores relationships between levels of estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, and testosterone (estimated using menstrual cycle information) and women’s preferences for male vocal masculinity in normally cycling and hormonally contracepting heterosexual females. Preferences for vocal masculinity decreased with predicted progesterone levels and increased with predicted prolactin levels in normally cycling—but not hormonally (...) contracepting—women. Adaptive explanations for menstrual variation in women’s preferences for masculine traits are discussed and evaluated in light of these findings. (shrink)

Human skin produces numerous neurohormones and neuropeptides. Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin‐releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1‐ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ. Since selected keratins are now understood to exert important regulatory functions beyond mechanical stability, we argue that neuroendocrine pathways of keratin regulation (...) are important for maintaining skin and hair follicle homeostasis. This invites innovative neuroendocrine therapeutic interventions for skin disorders characterized by abnormal keratin expression, ranging from psoriasis to genodermatoses, and for promoting skin wound healing and hair growth. This strategy can be probed in simple, but instructive and readily available human skin and hair follicle organ culture assays as ideal models for exploring this new neuroendocrine frontier in translational epithelial biology. (shrink)

The transcription of rat prolactin and growth hormone genes in vitro requires a pituitary transcription factor, specific to certain cell types in the pituitary, which currently appears to be the PUF‐I/Pit‐1/GHF‐1 protein. This factor binds to cis‐regulatory elements in the 5′ region of both genes and exerts a positive influence on transcription initiation presumably by interacting with general transcription factors. The PUF‐I/Pit‐1/GHF‐1 transcriptional regulatory protein probably has an important role in not only the differentiation of the pituitary lactotroph/somatotroph cell (...) lineage; it is also expressed in the early development of the nervous system but its function there is less well documented. It appears to be one member of a family of trans‐activator proteins involved in differential gene expression in several cell types. (shrink)

SummaryThe effects of infant suckling patterns on the post-partum resumption of ovulation and on birth-spacing are investigated among the Gainj of highland New Guinea. Based on hormonal evidence, the median duration of lactational anovulation is 20·4 months, accounting for about 75% of the median interval between live birth and next successful conception. Throughout lactation, suckling episodes are short and frequent, the interval changing slowly over time, from 24 minutes in newborns to 80 minutes in 3-year olds. Maternal serum prolactin (...) concentrations decline in parallel with the changes in suckling patterns, approaching the level observed in non-nursing women by about 24 months post-partum. A path analysis indicates that the interval between suckling episodes is the principal determinant of maternal prolactin concentration, with time since parturition affecting prolactin secretion only in so far as it affects suckling frequency. The extremely prolonged contraceptive effect of breast-feeding in this population thus appears to be due to a slow decline in suckling frequency with time since parturition and absence of a decline over time in hypothalamic–pituitary responsiveness to the suckling stimulus. (shrink)

In March 2022 the US Food and Drug Administration (FDA) published a risk assessment of a recent animal gene editing proposal submitted by Acceligen™. The proposal concerned the possibility of changing the cattle genome to obtain a slicker, shorter hair coat. Using CRISPR-Cas9 it was possible to introduce an intentional genomic alteration (IGA) to the prolactin receptor gene (PRLR), thereby producing PRLR-SLICK cattle. The goal was to diminish heat stress in the cattle by enhancing their heat-tolerance. With regard to (...) unintended alterations (i.e., off-target effects), the FDA stated that the IGA posed a low, but still present, risk to animal safety. The aim of this article is to present some initial insights into the welfare issues raised by PRLR-SLICK cattle by addressing the question: Do SLICK cattle have better welfare than non-SLICK cattle when exposed to heat stress? Two potential welfare concerns are examined. The first is pleiotropy, an issue that arises when one gene affects multiple traits. Given the pleiotropic nature of prolactin, it has been suggested that the IGA for SLICK cattle may also affect their hepatic and other functions. The second concern relates not primarily to direct effects on cattle health, but rather to the indirect risk that this more heat-tolerant animal would just be used in the livestock sector under farming conditions that are such that the net welfare improvement would be non-existent. (shrink)

The precocious induction in vivo and in culture of insect and amphibian metamorphosis by exogenous ecdysteroids and thyroid hormones, and its retardation or inhibition by juvenile hormone and prolactin, respectively, has allowed the analysis of such diverse processes of post‐embryonic development as morphogenesis, tissue remodelling, functional reorganization, and programmed cell death. Metamorphosis in vertebrates also shares many similarities with mammalian development in the late foetal and perinatal period. This review describes the regulation of expression of some of the ‘adult’ (...) gene products during metamorphosis in invertebrates and vertebrates. Recent studies on metamorphosis have revealed the important role played by auto‐induction of hormone receptor genes, based on which a model will be presented to explain the activation of ‘downstream’ genes which give rise to the adult phenotype. It will also be argued that metamorphosis is an ideal model for analyzing some of the major mechanisms governing post‐embryonic development. (shrink)

An extensive, and controversial, literature concluding that prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid hormones are critical immunoregulatory factors has accumulated. However, recent studies of mice deficient in the production of these hormones or expression of their receptors indicate that there are only a few instances in which these hormones are required for lymphocyte development or antigen responsiveness. Instead, a case is made that their primary role is to counteract the effects of negative immunoregulatory factors, (...) such as glucocorticoids, which are produced when the organism is subjected to major stressors. The immunoprotective actions of PRL, GH, IGF-I, and/or thyroid hormones in these instances may ensure immune system homeostasis and reduce the susceptibility to stress-induced disease. These immuno-enhancing effects could be exploited clinically in instances where the immune system is depressed due to illness or various treatment regimens. BioEssays 23:288–294, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Recent studies have yielded new insights into the critical importance of adequate vitamin D3 intake and metabolism. Investigations of the actions of 1,25‐dihydroxyvitamin D3 (calcitriol) on novel target tissues has revealed that this hormone has functions other than its recognized action in regulating blood calcium and phosphate levels. Reports have characterized calcitriol receptors and activities in organs and tissues as diverse as pancreas, skeletal and heart muscle, blood cells, brain, skin, pituitary, parathyroid, kidney, bone and intestine. These studies suggest functions (...) for calcitriol as varied as the regulation of insulin and prolactin secretion, muscle contractility, immune cell metabolism, melanin synthesis and differentiation of blood cells. This information may ultimately help us to understand the etiologies of several kinds of organ dysfunction and lead to the development of tissue‐specific agents for new therapies. (shrink)

It is posited that the initiating event of amphibian regeneration of a limb, is retrodifferentiation* of what are to become the developing cells of the blastema. These cells reiterate a larval or premetamorphic ontogenic repertoire, induced by elevated levels of prolactin with adequate innervation. Subsequent redifferentiation of the blastema cells occurs, controlled by thyroxine and innervation.This temporal displacement of cellular morphologic characters in regeneration should be looked upon as a function of the ability to reiterate larval characters and subsequently (...) metamorphose. If correct, this would explain why amphibians which metamorphose only once, lose the ability to postmetamorphically regenerate. An exception to this,Xenopus laevis, an anuran which can epimorphically regenerate, to some extent, will be discussed.[/p]. (shrink)