The Ventral Premammillary Nucleus Links Metabolic Cues and Reproduction

Donato, José; Elias, Carol F.

doi:10.3389/fendo.2011.00057

Cited by 33 publications

(32 citation statements)

References 158 publications

(200 reference statements)

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“…The connections of the PMV are consistent with functional data that suggest a possible role in mediating certain aspects of reproductive behavior and physiology (Akesson and Micevych, 1995;Taleisnik, 1978, 1980), and perhaps aggressive behavior as well (Van den Berg et al, 1983). More recently the PMV has been proposed as a hypothalamic site linking metabolic information and reproductive responses (Donato and Elias, 2011).…”

Section: Mammillary Regionmentioning

confidence: 99%

“…DIENCEPHALON, BASAL GANGLIA, AMYGDALA, AND SEPTUM 1998; Myers et al, 2009). Projections from the PMv to the anteroventral periventricular nucleus and the GnRH neurons, and to the paraventricular and arcuate nuclei, provide direct routes for conveying metabolic signals onto components of the neural pathways controlling reproduction and energy balance (Donato and Elias, 2011;Leshan et al, 2009).…”

Section: Figurementioning

confidence: 99%

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Organization of the Hypothalamus

Simerly

2015

The Rat Nervous System

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Section: Mammillary Regionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Organization of the Hypothalamus

Simerly

2015

The Rat Nervous System

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“…Beyond infertility, these models are also characterized by lactational incompetence (18, 35). There is no direct input of leptin on GnRH neurons (33), although there is now strong evidence that leptin-regulated neurons from the arcuate nucleus (ARC) and the ventral premammilary nucleus provide afferent inputs that regulate GnRH neurons (10,19,23). Two of leptin's known mediators are agouti gene-related peptide (AGRP) and neuropeptide Y (NPY), neuropeptides that are coexpressed with ␥-aminobutyric acid in neurons located medially within the hypothalamic ARC nucleus.…”

mentioning

confidence: 99%

Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction

Sheffer-Babila

Sun

Israel

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant (Lepr db/db ) females result in restoration of fertility and lactation despite the persistence of obesity and insulin resistance. The overarching hypothesis in the present study is that the absence or reduction of leptin's inhibition of AGRP/NPY neurons leads to suppression of GnRH release in cases of leptin signaling deficiency. Since TAC2 (NKB)-TAC3R signaling plays a role in puberty maturation and is modulated by metabolic status, the other aim of this study is to test whether TAC2/NKB neurons in ARC regulated by melanocortinergic signals herein affect leptin's action on puberty and reproduction. Our data showed that AGRP deficiency in Lepr db/db females restores normal timing of vaginal opening and estrous cycling, although uterine weight gain and mammary gland development are morphologically delayed. Nonetheless, Agrp Ϫ/Ϫ Lepr db/db females are fertile and sustain adequate nutrition of pups with lactation to weaning age. AGRP deficiency results in advanced vaginal opening in wild-type female mice. The postpubertal increase in hypothalamic TAC2 mRNA was not observed in Lepr db/db females, whereas AGRP deficiency restored it in Lepr db/db females. Additionally, MC4R activation with MTII induced FOS expression in TAC2 neurons, supporting the concept of melanocortinergic regulation of TAC2 neurons. These studies suggest that AGRP imposes an inhibitory effect on puberty and that TAC2 neurons may transmit melanocortinergic inhibition of GnRH neurons.agouti-related peptide; leptin; puberty; reproduction THE ONSET OF PUBERTY is the culmination of a subtle shift in balance of stimulatory and inhibitory neurotransmission within a complex neural network. Whereas the intrinsic pulsatility of GnRH neurons points toward a cell-autonomous function of gonadotropin-releasing hormone (GnRH) secretion, extrinsic signals are likely to be required to trigger activity in quiescent GnRH neurons. There is undoubtedly a link between metabolic status and GnRH activity (34). In the context of normal leptin signaling, a role has been implicated on the basis of a direct correlation between puberty onset and body weight (8, 16). Additionally, cases of defective leptin signaling in both humans and rodents result in hypogonadotropic hypogonadism (13). In a case report of a girl with leptin deficiency, treatment with leptin appeared to reverse the hypogonadal state (12). In cases of lipodystrophy with attendant hypoleptinemia, leptin therapy normalized pituitary hormone release (29) and restored menstrual cycles to all treat...

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“…The ventral premammilary nucleus (PMv) is part of the sexually dimorphic circuitry and expresses the nuclear estrogen receptor and is responsive to sexual odorant molecules (Donato and Elias, 2011; Leshan et al, 2009; Merchenthaler et al, 2004; Simerly et al, 1990). It also houses a dense population of leptin receptors, and was recently found to be important for leptin's stimulatory action on the neuroendocrine reproductive axis (Donato et al, 2011; Donato et al, 2009; Leshan et al, 2009).…”

Section: Leptinmentioning

confidence: 99%

Minireview: Metabolic control of the reproductive physiology: Insights from genetic mouse models

Bellefontaine

Elias

2014

Hormones and Behavior

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Over the past two decades, and in particular over the past 5-7 years, there has been a tremendous advancement in the understanding of the metabolic control of reproductive physiology. This has been in large part due to the advancement and refinement of gene targeting tools and techniques for molecular mapping. Yet despite the emergence of exciting and often times thought-provoking data through the use of new mouse models, the heavy reliance on gene targeting strategies has become fundamental in this process and thus caution must be exercised when interpreting results. This minireview article will explore the generation of new mouse models using genetic manipulation, such as viral vector delivery and the use of the Cre/loxP system, to investigate the role of circulating metabolic hormones in the coordination of reproductive physiology. In addition, we will also highlight some of the pitfalls in the use of genetic manipulation in the current paradigms. However, it has become clear that metabolic cues employ integrated and plastic neural circuits in order to modulate the neuroendocrine reproductive axis, and despite recent advances much remains to be elucidated about this circuitry.

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The Ventral Premammillary Nucleus Links Metabolic Cues and Reproduction

Cited by 33 publications

References 158 publications

Organization of the Hypothalamus

Organization of the Hypothalamus

Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction

Minireview: Metabolic control of the reproductive physiology: Insights from genetic mouse models

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