Pregnancy, parturition and lactation comprise a continuum of adaptive changes necessary for the development and maintenance of the offspring. The endocrine changes that are driven by the conceptus and are essential for the maintenance of pregnancy and are involved in the preparations for motherhood are outlined. These changes include large increases in the secretion of sex steroid hormones, and the secretion of peptide hormones that are unique to pregnancy. The ability of these pregnancy hormones to alter several aspects of brain function in pregnancy is considered, and the adaptive importance of some of these changes is discussed, for example in metabolic and body fluid adjustments, and the induction of maternal behavior. The importance of sex steroids in determining the timing of the various adaptive changes in preparing for parturition and maternal behavior is emphasized, and the concept that the actions of prolactin and oxytocin, quintessential mammalian motherhood neuropeptides, can serve to coordinate a spectrum of adaptive changes is discussed. The part played by oxytocin neurons and their regulatory mechanisms is reviewed to illustrate how neural systems involved in maternity are prepared in pregnancy via changes in phenotype, synaptic organization and in the relative importance of their different inputs, to function optimally when needed. For oxytocin neurons secreting from the posterior pituitary, important in parturition and essential in lactation, these changes include mechanisms to restrain their premature activation, and adaptations to support synchronized burst firing for pulsatile oxytocin secretion in response to stimulation via afferents from the birth canal, olfactory system or suckled nipples. Within the brain, expression of oxytocin receptors permits centrally released oxytocin to facilitate the expression of maternal behavior. Changes in other neuroendocrine systems are similarly extensive, leading to lactation, suppression of ovulation, reduced stress responses and increased appetite; these changes in lactation are driven by the suckling stimulus. The possible link between these adaptations and changes in cognition and mood in pregnancy and post partum are considered, as well as the dysfunctions that lead to common problems of depression and puerperal psychoses.

Brain preparations for maternity--adaptive changes in behavioral and neuroendocrine systems during pregnancy and lactation. An overview.

The complex mechanisms controlling human parturition involves mother, fetus, and placenta, and stress is a key element activating a series of physiological adaptive responses. Preterm birth is a clinical syndrome that shares several characteristics with term birth. A major role for the neuroendocrine mechanisms has been proposed, and placenta/membranes are sources for neurohormones and peptides. Oxytocin (OT) is the neurohormone whose major target is uterine contractility and placenta represents a novel source that contributes to the mechanisms of parturition. The CRH/urocortin (Ucn) family is another important neuroendocrine pathway involved in term and preterm birth. The CRH/Ucn family consists of four ligands: CRH, Ucn, Ucn2, and Ucn3. These peptides have a pleyotropic function and are expressed by human placenta and fetal membranes. Uterine contractility, blood vessel tone, and immune function are influenced by CRH/Ucns during pregnancy and undergo major changes at parturition. Among the others, neurohormones, relaxin, parathyroid hormone-related protein, opioids, neurosteroids, and monoamines are expressed and secreted from placental tissues at parturition. Preterm birth is the consequence of a premature and sustained activation of endocrine and immune responses. A preterm birth evidence for a premature activation of OT secretion as well as increased maternal plasma CRH levels suggests a pathogenic role of these neurohormones. A decrease of maternal serum CRH-binding protein is a concurrent event. At midgestation, placental hypersecretion of CRH or Ucn has been proposed as a predictive marker of subsequent preterm delivery. While placenta represents the major source for CRH, fetus abundantly secretes Ucn and adrenal dehydroepiandrosterone in women with preterm birth. The relevant role of neuroendocrine mechanisms in preterm birth is sustained by basic and clinic implications.

Neuroendocrine Mechanisms in Pregnancy and Parturition

Our understanding of the functions of oxytocin in mammals has recently been challenged by findings in transgenic mice in which the oxytocin gene has been knocked out. Mammals generally have only two posterior pituitary nonapeptide genes, for oxytocin and vasopressin, while some marsupials do not express oxytocin but do express a closely related peptide, mesotocin, which acts at the oxytocin receptor (Acher et al. 1995). Birds have arginine vasotocin and mesotocin (Acher et al. 1995), while among other vertebrates a subclass of cartilaginous fishes evidently produces oxytocin (Michel et al. 1993). Mice homozygous for deletion of exon 1 of the oxytocin gene, containing the oxytocin nonapeptide sequence, were produced by homologous recombination in mouse embryonic stem cells. Offspring from matings of the heterozygotes were in the correct Mendelian frequency, indicating no lethal developmental defects in the homozygotes, which later showed normal sexual maturation, with both males and females showing sexual behaviour and normal fertility (Nishimori et al. 1996). Young and colleagues (1996) used gene targeting to generate a mouse with most of the first intron and the last two of the three exons of the oxytocin gene eliminated. The amount of oxytocin gene transcripts in the supraoptic and paraventricular nuclei of homozygotes was 1% of the wild-type level, with less than 0·4% of the wild-type content of oxytocin in the pituitary gland, and no oxytocin detectable in blood plasma by RIA. In both types of oxytocin gene disablement, the only evident defect was a complete failure of postpartum homozygotes to transfer milk to the suckling young, which consequently did not survive unless the mothers were treated with exogenous oxytocin. Thus parturition and maternal behaviour proceeded without oxytocin, although these processes were not studied in detail. These findings are surprising in view of the vast literature on a wide range of species suggesting important roles for oxytocin in regulating gonadal function, in expression of sexual behaviour, in parturition and initiation of maternal behaviour as well as in lactation. It is appropriate to consider whether the results from the oxytocin knockout mice arise from peculiarities in the roles of oxytocin in the mouse in comparison with other species, or indicate redundancy in the mechanisms in which oxytocin normally has an important role; apart that is, from the milk-ejection reflex in which there is no evident redundancy, at least in the mouse.

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Sex, parturition and motherhood without oxytocin?

Steroid hormone control of myometrial contractility and parturition.

https://www.endo.theclinics.com/article/S0889-8529(05)00122-2/pdf

Endocrinology of parturition

Daily and hourly temporal association between Δ4-androstenedione - induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey☆☆☆★★★

James A. Winter

Papers

Daily and hourly temporal association between Δ4-androstenedione - induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey☆☆☆★★★