Hypothalamic Control of Prolactin Secretion, and the Multiple Reproductive Functions of Prolactin

Grattan, David R.; Tissier, Paul Le

doi:10.1016/b978-0-12-397175-3.00012-0

Cited by 25 publications

(26 citation statements)

References 837 publications

(830 reference statements)

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“…phosphorylation of STAT5 (pSTAT5) (13). We found that the number of MPOA neurons showing prolactin-induced pSTAT5 was relatively low in nonpregnant mice but markedly increased during lactation (Fig.…”

Section: Resultsmentioning

confidence: 93%

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Brown

Aoki

Ladyman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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127

147

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Pregnancy hormones, such as prolactin, sensitize neural circuits controlling parental interactions to induce timely activation of maternal behaviors immediately after parturition. While the medial preoptic area (MPOA) is known to be critical for maternal behavior, the specific role of prolactin in this brain region has remained elusive. Here, we evaluated the role of prolactin action in the MPOA using complementary genetic strategies in mice. We characterized prolactin-responsive neurons within the MPOA at different hormonal stages and delineated their projections in the brain. We found that MPOA neurons expressing prolactin receptors (Prlr) form the nexus of a complex prolactin-responsive neural circuit, indicating that changing prolactin levels can act at multiple sites and thus, impinge on the overall activity of a distributed network of neurons. Conditional KO of Prlr from neuronal subpopulations expressing the neurotransmitters GABA or glutamate within this circuit markedly reduced the capacity for prolactin action both in the MPOA and throughout the network. Each of these manipulations, however, produced only subtle impacts on maternal care, suggesting that this distributed circuit is robust with respect to alterations in prolactin signaling. In contrast, acute deletion of Prlr in all MPOA neurons of adult female mice resulted in profound deficits in maternal care soon after birth. All mothers abandoned their pups, showing that prolactin action on MPOA neurons is necessary for the normal expression of postpartum maternal behavior in mice. Our data establish a critical role for prolactin-induced behavioral responses in the maternal brain, ensuring survival of mammalian offspring.maternal behavior | prolactin | prolactin receptor | medial preoptic area M aternal care is critical to survival of dependent offspring in mammals. Seminal work from Rosenblatt (1), published 50 y ago, showed that maternal behavior can be exhibited in ovariectomized, hypophysectomized rats, suggesting an underlying neural basis that was not dependent on hormonal inputs. Subsequent studies have characterized a complex neural circuitry controlling parental interactions (2, 3), with distributed sites mediating different components of the behavior (4). While the neural circuit controlling maternal behavior is not thought to be dependent on hormonal inputs, it is clear that pregnancy hormones, particularly rising levels of estradiol, oxytocin, prolactin, and placental lactogen, coupled with an abrupt decrease in progesterone can sensitize the underlying circuitry to induce timely activation of maternal behaviors immediately after parturition (5). The medial preoptic area (MPOA) forms a critical nexus (2, 3), integrating a range of hormonal and sensory inputs into the maternal circuit.Within the complex hormonal milieu of pregnancy, the specific role of prolactin in maternal behavior has remained elusive. This is largely because prolactin and the related placental lactogen have an obligate role in sustaining ovarian progesterone productio...

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Section: Resultsmentioning

confidence: 93%

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Brown

Aoki

Ladyman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

127

147

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“…Prolactin secretion from lactotrophs is tonically inhibited by dopamine produced from the tuberoinfundibular dopamine (TIDA) neurones in the arcuate nucleus . Prolactin acts to stimulate dopamine release from these neurones to regulate its own secretion, thus creating a short‐loop feedback system.…”

Section: Discussionmentioning

confidence: 99%

“…Prolactin is a hormone produced by lactotroph cells in the anterior pituitary and its major function is to stimulate milk production during lactation. Prolactin has been implicated in a broad range of functions in the brain and it has been proposed that many of these functions are involved in adaptive changes seen in the mother during pregnancy to prepare her for lactation . In particular, prolactin plays a role in energy homeostasis and evidence from rats indicates that prolactin can stimulate food intake and increase body weight .…”

Section: Introductionmentioning

confidence: 99%

“…Prolactin has been implicated in a broad range of functions in the brain 1 and it has been proposed that many of these functions are involved in adaptive changes seen in the mother during pregnancy to prepare her for lactation. 2 In particular, prolactin plays a role in energy homeostasis and evidence from rats indicates that prolactin can stimulate food intake and increase body weight. [3][4][5] Administration of prolactin into the cerebral ventricles can increase food intake 6 and this orexigenic effect is independent of ovarian steroids.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prolactin receptors in Rip‐cre cells, but not in AgRP neurones, are involved in energy homeostasis

Ladyman

MacLeod

Aung

et al. 2017

J Neuroendocrinology

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Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The present study aimed to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and whether they can mediate the effects of prolactin on energy homeostasis. To determine whether Agrp neurones or Rip-Cre neurones are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurones (td-tomato/Agrp-Cre) or Rip-Cre neurones (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labelled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signalling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlr mice). The Prlr construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of green fluorescent protein (GFP) in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localised with td-tomato, indicating that there is a subpopulation of Rip-Cre neurones in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurones had lower body weights, increased oxygen consumption, increased running wheel activity and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurones. By contrast, no co-localisation of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice after prolactin treatment. Moreover, Prlr /Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to littermate controls. Overall, these results indicate that Rip-Cre neurones in the arcuate nucleus are responsive to prolactin and may play a role in the orexigenic effects of prolactin, whereas prolactin does not directly affect Agrp neurones.

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“…59 It was recognised early on that the PRL receptor was a member of the cytokine family of receptors, 60 (Figure 4). 63,64 In parallel with these studies on the receptor, a transcription factor known as "mammary gland factor" was identified, and shown to be critical to mediating the actions of PRL on gene expression in the mammary gland. 64 Soon after, "mammary gland factor" was identified to be a member of the cytokine-regulated STAT family of proteins, and it was assigned the name STAT5.…”

Section: Neuro Chemi C Al Ac Ti On S Of Pro L Ac Tinmentioning

confidence: 98%

30 years after: CNS actions of prolactin: Sources, mechanisms and physiological significance

Bridges

Grattan

2019

J Neuroendocrinology

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Our understanding of the neural actions of prolactin (PRL) and its biochemical basis has expanded greatly over the past three decades. During this time, major progress has been made, including clarification of how PRL accesses the brain, identification of the PRL receptor and the sites where it is expressed within the brain, determination of the neurochemical mechanism of action of PRL and its effect on genomic expression in neurones, identification of the neural sites where PRL acts to stimulate maternal behaviour and related affective states, and exploration of how life experiences impact neural PRL receptor activity and actions. The next 30 years promise to reveal a myriad of basic and clinical findings regarding new roles for PRL and a greater indepth understanding of how and where PRL affects physiological and behavioural processes.

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Hypothalamic Control of Prolactin Secretion, and the Multiple Reproductive Functions of Prolactin

Cited by 25 publications

References 837 publications

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

Prolactin receptors in Rip‐cre cells, but not in AgRP neurones, are involved in energy homeostasis

30 years after: CNS actions of prolactin: Sources, mechanisms and physiological significance

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