Synchrony, a construct used across multiple fields to denote the temporal relationship between events, is applied to the study of parent-infant interactions and suggested as a model for intersubjectivity. Three types of timed relationships between the parent and child's affective behavior are assessed: concurrent, sequential, and organized in an ongoing patterned format, and the development of each is charted across the first year. Viewed as a formative experience for the maturation of the social brain, synchrony impacts the development of self-regulation, symbol use, and empathy across childhood and adolescence. Different patterns of synchrony with mother, father, and the family and across cultures describe relationship-specific modes of coordination. The capacity to engage in temporally-matched interactions is based on physiological mechanisms, in particular oscillator systems, such as the biological clock and cardiac pacemaker, and attachment-related hormones, such as oxytocin. Specific patterns of synchrony are described in a range of child-, parent- and context-related risk conditions, pointing to its ecological relevance and usefulness for the study of developmental psychopathology. A perspective that underscores the organization of discrete relational behaviors into emergent patterns and considers time a central parameter of emotion and communication systems may be useful to the study of interpersonal intimacy and its potential for personal transformation across the lifespan.

Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions.

Psychopharmacology: The Fourth Generation of Progress.

Gender differences in autoimmune disease.

The endocrine system coordinates development of the mammary gland with reproductive development and the demand of the offspring for milk. Three categories of hormones are involved. The levels of the reproductive hormones, estrogen, progesterone, placental lactogen, prolactin, and oxytocin, change during reproductive development or function and act directly on the mammary gland to bring about developmental changes or coordinate milk delivery to the offspring. Metabolic hormones, whose main role is to regulate metabolic responses to nutrient intake or stress, often have direct effects on the mammary gland as well. The important hormones in this regard are growth hormone, corticosteroids, thyroid hormone, and insulin. A third category of hormones has recently been recognized, mammary hormones. It currently includes growth hormone, prolactin, PTHrP, and leptin. Because a full-term pregnancy in early life is associated with a reduction in breast carcinogenesis, an understanding of the mechanisms by which these hormones bring about secretory differentiation may offer clues to the prevention of breast cancer.

Hormonal regulation of mammary differentiation and milk secretion.

Procreation is essential for survival of species. Not surprisingly, complex neuronal networks have evolved to mediate the diverse internal and external environmental inputs that regulate reproduction in vertebrates. Ultimately, these regulatory factors impinge, directly or indirectly, on a final common pathway, the neurons producing the gonadotropin-releasing hormone (GnRH), which stimulates pituitary gonadotropin secretion and thereby gonadal function. Compelling evidence, accumulated in the last few years, has revealed that kisspeptins, a family of neuropeptides encoded by the Kiss1 gene and produced mainly by neuronal clusters at discrete hypothalamic nuclei, are pivotal upstream regulators of GnRH neurons. As such, kisspeptins have emerged as important gatekeepers of key aspects of reproductive maturation and function, from sexual differentiation of the brain and puberty onset to adult regulation of gonadotropin secretion and the metabolic control of fertility. This review aims to provide a comprehensive account of the state-of-the-art in the field of kisspeptin physiology by covering in-depth the consensus knowledge on the major molecular features, biological effects, and mechanisms of action of kisspeptins in mammals and, to a lesser extent, in nonmammalian vertebrates. This review will also address unsolved and contentious issues to set the scene for future research challenges in the area. By doing so, we aim to endow the reader with a critical and updated view of the physiological roles and potential translational relevance of kisspeptins in the integral control of reproductive function.

Kisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms

The neuroendocrine control of prolactin secretion is unlike that of any other pituitary hormone. It is predominantly inhibited by the hypothalamus and, in the absence of a regulatory feedback hormone, it acts directly in the brain to suppress its own secretion. In addition to this short-loop feedback action in the brain, prolactin has been reported to influence a wide range of other brain functions. There have been few attempts to rationalise why a single hormone might exert such a range of distinct and seemingly unrelated neuroendocrine functions. In this review, we highlight some of the original studies that first characterised the unusual features of prolactin neuroendocrinology, and then attempt to identify areas of new progress and/or controversy. Finally, we discuss a hypothesis that provides a unifying explanation for the pleiotrophic actions of prolactin in the brain.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01736.x

Prolactin: a pleiotropic neuroendocrine hormone.

Prolactin has numerous biological actions in the brain, and transgenic mice are increasingly being used to investigate these actions. The present study aimed to provide a detailed mapping of the prolactin-responsive neurons in the female mouse forebrain by describing the distribution of prolactin receptor mRNA by in situ hybridization, and measuring prolactin-induced phosphorylation of signal transducer and activation of transcription 5 (pSTAT5) by immunohistochemistry. For in situ hybridization, a probe designed to detect both long and short receptor isoforms showed mRNA expression in a heterogeneous manner within the forebrain. Strong expression was observed in the rostral hypothalamus, particularly in periventricular regions, as well as in the arcuate and ventromedial nuclei of the mediobasal hypothalamus. There was also significant expression in some nonhypothalamic regions, notably high expression in the choroid plexus, and lower levels of expression in the medial amygdala, bed nucleus of the stria terminalis, and lateral septum. Prolactin-induced pSTAT5, detected by immunohistochemistry, provided a functional index of prolactin receptor activation in neurons. Prolactin-induced pSTAT5 was only observed in areas containing prolactin receptor mRNA, and was particularly prominent in the rostral and mediobasal hypothalamus. Most other areas that contained prolactin receptor mRNA also showed positive signal for prolactin-induced pSTAT5. The major exceptions were paraventricular nucleus and median preoptic nucleus, in which prolactin receptor mRNA was observed, but no induction of pSTAT5 by prolactin. The data provide key neuroanatomical information facilitating the use of the mouse model for furthering our understanding of prolactin actions in the brain.

Distribution of prolactin-responsive neurons in the mouse forebrain.

During pregnancy, neuroendocrine control of prolactin secretion is markedly altered to allow a state of hyperprolactinaemia to develop. Prolactin secretion is normally tightly regulated by a short-loop negative-feedback mechanism, whereby prolactin stimulates activity of tuberoinfundibular dopamine (TIDA) neurones to increase dopamine secretion into the pituitary portal blood. Dopamine inhibits prolactin secretion, thus reducing prolactin concentrations in the circulation back to the normal low level. Activation of this feedback secretion by placental lactogen during pregnancy maintains relatively low levels of prolactin secretion during early and mid-pregnancy. Despite the continued presence of placental lactogen, however, dopamine secretion from TIDA neurones is reduced during late pregnancy. Moreover, the neurones become completely unresponsive to endogenous or exogenous prolactin at this time, allowing a large nocturnal surge of prolactin to occur from the maternal pituitary gland during the night before parturition. In this review, we describe the changing patterns of prolactin secretion during pregnancy in the rat, and discuss the neuroendocrine mechanisms controlling these changes. The loss of response to prolactin is an important maternal adaptation to pregnancy, allowing the prolonged period of hyperprolactinaemia required for mammary gland development and function and for maternal behaviour immediately after parturition, and possibly also contributing to a range of other adaptive responses in the mother.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01661.x

Pregnancy-Induced Adaptation in the Neuroendocrine Control of Prolactin Secretion

Male pheromones initiate prolactin-induced neurogenesis and advance maternal behavior in female mice

Prolactin receptor mRNA is expressed in GABA and kisspeptin neurons in the rostral hypothalamus but in relatively few GnRH neurons, suggesting that hyperprolactinemia might cause infertility through actions on afferent inputs to GnRH neurons.

/pdf/identification-of-prolactin-sensitive-gaba-and-kisspeptin-3pzjdu51lb.pdf

Ilona C. Kokay

Papers

Prolactin: a pleiotropic neuroendocrine hormone.

Distribution of prolactin-responsive neurons in the mouse forebrain.

Pregnancy-Induced Adaptation in the Neuroendocrine Control of Prolactin Secretion

Male pheromones initiate prolactin-induced neurogenesis and advance maternal behavior in female mice

Identification of prolactin-sensitive GABA and kisspeptin neurons in regions of the rat hypothalamus involved in the control of fertility.