scholarly journals Hypothalamic pathways linking energy balance and reproduction

2008 ◽  
Vol 294 (5) ◽  
pp. E827-E832 ◽  
Author(s):  
Jennifer W. Hill ◽  
Joel K. Elmquist ◽  
Carol F. Elias
Keyword(s):  
Energy Balance ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Metabolic Stress ◽  
Reproductive Function ◽  
Reproductive Axis ◽  
Hypothalamic Nuclei ◽  
Adiposity Signals ◽  
The Brain

During periods of metabolic stress, animals must channel energy toward survival and away from processes such as reproduction. The reproductive axis, therefore, has the capacity to respond to changing levels of metabolic cues. The cellular and molecular mechanisms that link energy balance and reproduction, as well as the brain sites mediating this function, are still not well understood. This review focuses on the best characterized of the adiposity signals: leptin and insulin. We examine their reproductive role acting on the classic metabolic pathways of the arcuate nucleus, NPY/AgRP and POMC/CART neurons, and the newly identified kisspeptin network. In addition, other hypothalamic nuclei that may play a role in linking metabolic state and reproductive function are discussed. The nature of the interplay between these elements of the metabolic and reproductive systems presents a fascinating puzzle, whose pieces are just beginning to fall into place.

scholarly journals Kisspeptin and energy balance in reproduction

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. R53-R63 ◽  
Author(s):  
Julie-Ann P De Bond ◽  
Jeremy T Smith
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Arcuate Nucleus ◽  
Reproductive Function ◽  
Neuroendocrine Regulation ◽  
Direct Role ◽  
Gnrh Neurons ◽  
The Brain ◽  
Direct Regulator

Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as isKiss1expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data fromKiss1rknockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

Oestrogenic action of neonatal tamoxifen on the hypothalamus and reproductive system in female mice

2017 ◽  
Vol 29 (5) ◽  
pp. 1012 ◽  
Author(s):  
Rahmatollah Parandin ◽  
Morteza Behnam-Rassouli ◽  
Nasser Mahdavi-Shahri
Keyword(s):  
Reproductive System ◽  
Reproductive Function ◽  
Female Mice ◽  
Treatment And Prevention ◽  
Receptor Modulator ◽  
Neuron Populations ◽  
Reproductive Axis ◽  
First Time ◽  
The Brain ◽  
Selective Oestrogen Receptor Modulator

Tamoxifen, a selective oestrogen receptor modulator, is widely used for both the treatment and prevention of breast cancer in women; however, it is known to have adverse effects in the female reproductive system. Growing evidence suggests that oestrogen-sensitive neuron populations of the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset and reproductive function. The aim of the present study was to evaluate whether neonatal exposure to tamoxifen affects oestrogenic actions in the brain and reproductive function in mice. On 1 to 5 postnatal days, female pups were injected subcutaneously with sesame oil (sham), oestradiol benzoate (EB; 20 µg kg–1), tamoxifen (0.4 mg kg–1) or EB+tamoxifen. Control mice received no treatment. Mice in the EB, tamoxifen and tamoxifen+EB groups exhibited advanced vaginal opening, disrupted oestrous cycles and a decreased follicular pool. Conversely, in these groups, there was a reduction in kisspeptin (Kiss1) mRNA expression, the neuronal density of AVPV and ARC nuclei and LH and oestradiol concentrations in the serum. The results of the present study confirm oestrogenic actions of tamoxifen in the brain and reproductive system. In addition, we show, for the first time, that tamoxifen has oestrogenic effects on the oestrogen-sensitive hypothalamic AVPV and ARC nuclei controlling the reproductive axis in female mice.

Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract

2007 ◽  
Vol 292 (5) ◽  
pp. E1348-E1357 ◽  
Author(s):  
Mario Perello ◽  
Ronald C. Stuart ◽  
Eduardo A. Nillni
Keyword(s):  
Energy Balance ◽  
Arcuate Nucleus ◽  
Transcriptional Level ◽  
Solitary Tract ◽  
Energy Status ◽  
Melanocyte Stimulating Hormone ◽  
Pomc Mrna ◽  
Induced Changes ◽  
The Brain ◽  
Processing Mechanism

The α-melanocyte-stimulating hormone (α-MSH), derived from proopiomelanocortin (POMC), is generated by a posttranslational processing mechanism involving the prohormone convertases (PCs) PC1/3 and PC2. In the brain, α-MSH is produced in the arcuate nucleus (ARC) of the hypothalamus and in the nucleus of the solitary tract (NTS) of the medulla. This peptide is key in controlling energy balance, as judged by changes observed at transcriptional level. However, little information is available regarding the biosynthesis of the precursor POMC and the production of its processed peptides during feeding, fasting, and fasting plus leptin in the ARC compared with the NTS in conjunction with the PC activity. In this study we found that, in the ARC, pomc mRNA, POMC-derived peptides, and PC1/3 all decreased during fasting, and administration of leptin reversed these effects. In contrast, in the NTS, where there is a large amount of a 28.1-kDa peptide similar in size to POMC, the 28.1-kDa peptide and other POMC-derived peptides, including α-MSH, were further accumulated in fasting conditions, whereas pomc mRNA decreased. These changes were not reversed by leptin. We also observed that, during fasting, PC2 levels decreased in the NTS. These data suggest that, in the NTS, fasting induced changes in POMC biosynthesis, and processing is independent of leptin. These observations indicate that changes in energy status affect POMC in the brain in a tissue-specific manner. This represents a novel aspect in the regulation of energy balance and may have implications in the pathophysiology of obesity.

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

2010 ◽  
Vol 299 (1) ◽  
pp. E54-E61 ◽  
Author(s):  
J. M. Castellano ◽  
A. H. Bentsen ◽  
M. Romero ◽  
R. Pineda ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Food Intake ◽  
Acute Inflammation ◽  
Arcuate Nucleus ◽  
Metabolic Stress ◽  
Reproductive Function ◽  
Male Rats ◽  
Inflammatory Phase ◽  
Gonadotropic Function ◽  
Gonadotropic Axis ◽  
The Impact

Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.

329. IS THERE VARIATION IN THE LEVEL OF INPUT OF KISSPEPTIN TERMINALS ONTO GnRH NEURONS ACROSS THE EQUINE OESTROUS CYCLE?

2010 ◽  
Vol 22 (9) ◽  
pp. 129
Author(s):  
C. J. Scott ◽  
C. A. Setterfield ◽  
A. Caraty ◽  
S. T. Norman
Keyword(s):  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Reproductive Function ◽  
Oestrous Cycle ◽  
Gnrh Neurons ◽  
Gonadotrophin Releasing Hormone ◽  
Potential Interactions ◽  
Lh Secretion ◽  
The Brain ◽  
Dual Label

Kisspeptin (KP) plays a key role in reproductive function including the regulation of gonadotrophin releasing hormone (GnRH) and luteinising hormone (LH) secretion in many species but little is known about its role in the mare. In this study, we examined the location of KP-producing neurons in the brain of the mare, their potential interactions with GnRH neurons, and temporal changes in their expression across the oestrous cycle. Mares (n = 3/group) were killed at oestrus (just prior to ovulation), mid-dioestrus, and late dioestrus and the head was perfusion fixed with paraformaldehyde, and hypothalamus collected. Coronal sections (40 μm) were used for dual-label immuno-stained for KP & GnRH. The majority of KP-immunoreactive (-ir) neurons were located in the arcuate nucleus/median eminence (especially mid and caudal regions), and periventricular nucleus. There was a trend (P = 0.09) towards increasing numbers of KP-ir neurons across the cycle. GnRH-ir neurons, located primarily in the arcuate nucleus (especially mid arcuate), as well as the preoptic area, did not change in number across the cycle. Numerous interactions between KP and GnRH neurons were observed, primarily in the arcuate nucleus; KP fibres interacting with GnRH cell bodies, fibre-fibre interactions between KP and GnRH, and GnRH fibres interacting with KP cell bodies. Overall we found KP inputs to 32% of GnRH-ir cells, but the number of these interactions did not vary across the oestrous cycle. This study has confirmed the reciprocal innervation between KP & GnRH neurons in the mare. Although we did not detect variation in the degree across the oestrous cycle this may reflect the sample size issues inherent to equine research.

scholarly journals Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose

2020 ◽  
Vol 105 (5) ◽  
pp. 1538-1551
Author(s):  
Angela Delaney ◽  
Rita Volochayev ◽  
Brooke Meader ◽  
Janice Lee ◽  
Konstantinia Almpani ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Normal Breast ◽  
Breast Development ◽  
Reproductive Axis ◽  
Gnrh Neurons ◽  
Male Patients ◽  
And Function ◽  
Human Embryology ◽  
The Brain ◽  
Insight Into

Abstract Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Cross-talk between estrogen and leptin signaling in the hypothalamus

2008 ◽  
Vol 294 (5) ◽  
pp. E817-E826 ◽  
Author(s):  
Qian Gao ◽  
Tamas L. Horvath
Keyword(s):  
Energy Balance ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Steroid Hormone ◽  
The United States ◽  
Gonadal Steroid ◽  
Leptin Signaling ◽  
Downstream Signaling ◽  
Reproductive Axis ◽  
The Brain

Obesity, characterized by enhanced food intake (hyperphagia) and reduced energy expenditure that results in the accumulation of body fat, is a major risk factor for various diseases, including diabetes, cardiovascular disease, and cancer. In the United States, more than half of adults are overweight, and this number continues to increase. The adipocyte-secreted hormone leptin and its downstream signaling mediators play crucial roles in the regulation of energy balance. Leptin decreases feeding while increasing energy expenditure and permitting energy-intensive neuroendocrine processes, such as reproduction. Thus, leptin also modulates the neuroendocrine reproductive axis. The gonadal steroid hormone estrogen plays a central role in the regulation of reproduction and also contributes to the regulation of energy balance. Estrogen deficiency promotes feeding and weight gain, and estrogen facilitates, and to some extent mimics, some actions of leptin. In this review, we examine the functions of estrogen and leptin in the brain, with a focus on mechanisms by which leptin and estrogen cooperate in the regulation of energy homeostasis.

Kisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms

2012 ◽  
Vol 92 (3) ◽  
pp. 1235-1316 ◽  
Author(s):  
Leonor Pinilla ◽  
Enrique Aguilar ◽  
Carlos Dieguez ◽  
Robert P. Millar ◽  
Manuel Tena-Sempere
Keyword(s):  
Biological Effects ◽  
Reproductive Function ◽  
Future Research ◽  
Gonadotropin Secretion ◽  
Integral Control ◽  
Molecular Features ◽  
Hypothalamic Nuclei ◽  
Key Aspects ◽  
And Function ◽  
The Brain

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.

scholarly journals Shiftwork and Light at Night Negatively Impact Molecular and Endocrine Timekeeping in the Female Reproductive Axis in Humans and Rodents

2020 ◽  
Vol 22 (1) ◽  
pp. 324
Author(s):  
Alexandra Yaw ◽  
Autumn McLane-Svoboda ◽  
Hanne Hoffmann
Keyword(s):  
Molecular Mechanisms ◽  
Negative Impact ◽  
Reproductive Function ◽  
Rodent Models ◽  
Light At Night ◽  
Reproductive Dysfunction ◽  
Shift Workers ◽  
Reproductive Axis ◽  
Light Shifts ◽  
The Impact

Shiftwork, including work that takes place at night (nightshift) and/or rotates between day and nightshifts, plays an important role in our society, but is associated with decreased health, including reproductive dysfunction. One key factor in shiftwork, exposure to light at night, has been identified as a likely contributor to the underlying health risks associated with shiftwork. Light at night disrupts the behavioral and molecular circadian timekeeping system, which is important for coordinated timing of physiological processes, causing mistimed hormone release and impaired physiological functions. This review focuses on the impact of shiftwork on reproductive function and pregnancy in women and laboratory rodents and potential underlying molecular mechanisms. We summarize the negative impact of shiftwork on female fertility and compare these findings to studies in rodent models of light shifts. Light-shift rodent models recapitulate several aspects of reproductive dysfunction found in shift workers, and their comparison with human studies can enable a deeper understanding of physiological and hormonal responses to light shifts and the underlying molecular mechanisms that may lead to reproductive disruption in human shift workers. The contributions of human and rodent studies are essential to identify the origins of impaired fertility in women employed in shiftwork.

scholarly journals Central Regulation of Metabolism by Growth Hormone

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 129
Author(s):  
Jose Donato ◽  
Frederick Wasinski ◽  
Isadora C. Furigo ◽  
Martin Metzger ◽  
Renata Frazão
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Metabolic Stress ◽  
Wide Distribution ◽  
Tissue Growth ◽  
Neuronal Populations ◽  
Hypothalamic Nuclei ◽  
The Brain

Growth hormone (GH) is secreted by the pituitary gland, and in addition to its classical functions of regulating height, protein synthesis, tissue growth, and cell proliferation, GH exerts profound effects on metabolism. In this regard, GH stimulates lipolysis in white adipose tissue and antagonizes insulin’s effects on glycemic control. During the last decade, a wide distribution of GH-responsive neurons were identified in numerous brain areas, especially in hypothalamic nuclei, that control metabolism. The specific role of GH action in different neuronal populations is now starting to be uncovered, and so far, it indicates that the brain is an important target of GH for the regulation of food intake, energy expenditure, and glycemia and neuroendocrine changes, particularly in response to different forms of metabolic stress such as glucoprivation, food restriction, and physical exercise. The objective of the present review is to summarize the current knowledge about the potential role of GH action in the brain for the regulation of different metabolic aspects. The findings gathered here allow us to suggest that GH represents a hormonal factor that conveys homeostatic information to the brain to produce metabolic adjustments in order to promote energy homeostasis.

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