An updated view of hypothalamic–vascular–pituitary unit function and plasticity

Tissier, Paul Le; Campos, Pauline; Lafont, Chrystel; Romanò, Nicola; Hodson, David J.; Mollard, Patrice

doi:10.1038/nrendo.2016.193

Cited by 92 publications

(82 citation statements)

References 144 publications

(149 reference statements)

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“…For most hormones, this pulsatility is thought to be generated by episode generators located within the hypothalamus and pituitary gland (1,2). However, with few exceptions, it has been extremely difficult to determine the identity and nature of these neuroendocrine pulse generators (3,4).…”

mentioning

confidence: 99%

Definition of the hypothalamic GnRH pulse generator in mice

Clarkson

Han

Piet

et al. 2017

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

312

287

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The pulsatile release of luteinizing hormone (LH) is critical for mammalian fertility. However, despite several decades of investigation, the identity of the neuronal network generating pulsatile reproductive hormone secretion remains unproven. We use here a variety of optogenetic approaches in freely behaving mice to evaluate the role of the arcuate nucleus kisspeptin (ARN KISS ) neurons in LH pulse generation. Using GCaMP6 fiber photometry, we find that the ARN KISS neuron population exhibits brief (∼1 min) synchronized episodes of calcium activity occurring as frequently as every 9 min in gonadectomized mice. These ARN KISS population events were found to be near-perfectly correlated with pulsatile LH secretion. The selective optogenetic activation of ARN KISS neurons for 1 min generated pulses of LH in freely behaving mice, whereas inhibition with archaerhodopsin for 30 min suppressed LH pulsatility. Experiments aimed at resetting the activity of the ARN KISS neuron population with halorhodopsin were found to reset ongoing LH pulsatility. These observations indicate the ARN KISS neurons as the long-elusive hypothalamic pulse generator driving fertility.fertility | GnRH | kisspeptin | pulse | arcuate nucleus

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mentioning

confidence: 99%

Definition of the hypothalamic GnRH pulse generator in mice

Clarkson

Han

Piet

et al. 2017

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

312

287

View full text Add to dashboard Cite

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“…These findings show that additional inhibitory input was required to maintain PRL levels in the absence of autoregulatory PRL feedback and that a fully functioning hypothalamic feedback can compensate for the absence of pituitary autoregulation. The data suggest, however, that in physiologic situations in which dopamine output is impaired, such as during lactation (30,31) or aging (32), pituitary autoregulation may be important to minimize the occurrence of adenomas.…”

Section: Discussionmentioning

confidence: 97%

Autocrine actions of prolactin contribute to the regulation of lactotroph function in vivo

et al. 2018

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Prolactin (PRL), whose principal role is regulation of lactation, is mainly synthesized and secreted by lactotroph anterior pituitary cells. Its signaling is exerted via a transmembrane PRL receptor (PRLR) expressed in a wide variety of tissues, including the anterior pituitary. Dopamine, which is secreted by tuberoinfundibular hypothalamic neurons, is the major inhibitory regulator of prolactin secretion. Although PRL is well established to stimulate hypothalamic dopamine secretion, thereby exerting a negative feedback regulation on its own release, autocrine or paracrine actions of PRL on lactotroph cells have also been suggested. Within the pituitary, PRL may inhibit both lactotroph proliferation and secretion, but in vivo evaluation of these putative functions is limited. To determine whether the autocrine actions of prolactin have a significant role in the physiologic function of lactotrophs in vivo, we examined the consequences of conditional deletion of Prlr in lactotroph cells using a novel mouse line with loxP sites flanking the Prlr gene ( Prlr) and Cre-recombinase (Cre) expressed under the control of the pituitary-specific Prl promoter. Prlr/Prl-Cre mice have normal PRL levels and did not develop any pituitary lactotroph adenoma, even at 20 mo of age. Nevertheless, Prlr/Prl-Cre mice displayed an increased dopaminergic inhibitory tone compared with control Prlr mice. These results elegantly confirm an autocrine/paracrine feedback of PRL on lactotroph cells in vivo, which can be fully compensated by an intact hypothalamic feedback system.-Bernard, V., Lamothe, S., Beau, I., Guillou, A., Martin, A., Le Tissier, P., Grattan, D., Young, J., Binart, N. Autocrine actions of prolactin contribute to the regulation of lactotroph function in vivo.

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“…Several inhibitory and stimulatory factors control the release of PRL, although the most important site of regulation resides in the neuroendocrine dopaminergic neurones (NEDA) of the medial basal hypothalamus, the majority of which are located in the arcuate nucleus of the hypothalamus (ARH) . NEDA neurones inhibit the production and release of PRL by lactotrophs via dopamine transmission into the blood in response to PRL itself.…”

Section: Introductionmentioning

confidence: 99%

“…NEDA neurones inhibit the production and release of PRL by lactotrophs via dopamine transmission into the blood in response to PRL itself. Suppression of dopamine discharge by NEDA neurones leads to disinhibition of lactotrophs, which quickly release PRL into circulation, thus establishing a self‐inhibitory feedback loop …”

Section: Introductionmentioning

confidence: 99%

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Sexually dimorphic neuronal inputs to the neuroendocrine dopaminergic system governing prolactin release

Esteves

Matias

Mendes

et al. 2019

J Neuroendocrinology

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Prolactin (PRL) is a pleiotropic hormone that was identified in the context of maternal care and its release from the anterior pituitary is primarily controlled by neuroendocrine dopaminergic (NEDA) neurones of the arcuate nucleus of the hypothalamus. The sexually dimorphic nature of PRL physiology and associated behaviours is evident in mammals, even though the number and density of NEDA neurones is reported as not being sexually dimorphic in rats. However, the underlying circuits controlling NEDA neuronal activity and subsequent PRL release are largely uncharacterised. Thus, we mapped whole‐brain monosynaptic NEDA inputs in male and female mice. Accordingly, we employed a rabies virus based monosynaptic tracing system capable of retrogradely mapping inputs into genetically defined neuronal populations. To gain genetic access to NEDA neurones, we used the dopamine transporter promoter. Here, we unravel 59 brain regions that synapse onto NEDA neurones and reveal that male and female mice, despite monomorphic distribution of NEDA neurones in the arcuate nucleus of the hypothalamus, receive sexually dimorphic amount of inputs from the anterior hypothalamic nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular hypothalamic nucleus, posterior periventricular nucleus, supraoptic nucleus, suprachiasmatic nucleus, lateral supramammillary nucleus, tuberal nucleus and periaqueductal grey. Beyond highlighting the importance of considering sex as a biological variable when evaluating connectivity in the brain, these results illustrate a case where a neuronal population with similar anatomical distribution has a subjacent sexually dimorphic connectivity pattern, potentially capable of contributing to the sexually dimorphic nature of PRL release and function.

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An updated view of hypothalamic–vascular–pituitary unit function and plasticity

Abstract: The discoveries of novel functional adaptations of the hypothalamus and anterior pituitary gland for physiological regulation have transformed our understanding of their interaction. The activity of a small proportion of hypothalamic neurons can

Cited by 92 publications

References 144 publications

Definition of the hypothalamic GnRH pulse generator in mice

Definition of the hypothalamic GnRH pulse generator in mice

Autocrine actions of prolactin contribute to the regulation of lactotroph function in vivo

Sexually dimorphic neuronal inputs to the neuroendocrine dopaminergic system governing prolactin release

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