Regulators and Integration of Peripheral Signals

2021 ◽  
Author(s):  
Michelle T. Foster
Keyword(s):  
Adipose Tissue ◽  
Reproductive Function ◽  
Energy Regulation ◽  
Energy Status ◽  
Peripheral Tissues ◽  
Reproductive Axis ◽  
Reproductive Events ◽  
Ovarian Cyclicity ◽  
Reproductive Processes ◽  
The Brain

In mammals, reproductive function is closely regulated by energy availability. It is influenced by both extremes of nutrition, too few calories (undernutrition) and an excessive amount of calories (obesity). Atypical decreases or increases in weight can have adverse effects on the reproductive axis. This includes suppression of reproductive function, decreases in ovarian cyclicity, reduction in fertility, anovulation, and dysregulation of spermatogenesis. The balance between energy regulation and reproduction is supervised by a complex system comprised of the brain and peripheral tissues. The brain senses and integrates various systemic and central signals that are indicative of changes in body physiology and energy status. This occurs via numerous factors, including metabolic hormones and nutrients. Adipokines, endocrine factors primarily secreted by white adipose tissue, and adipose tissue related cytokines (adipocytokines) contribute to the regulation of maturity, fertility, and reproduction. Indeed, some adipokines play a fundamental role in reproductive disorders. The brain, predominantly the hypothalamus, is responsible for linking adipose-derived signals to pathways controlling reproductive processes. Gonadotropin-releasing hormone (GnRH) cells in the hypothalamus are fundamental in relaying adipose-derived signals to the pituitary–gonadal axis, which consequently controls reproductive processes. Leptin, adiponectin, apelin, chermin, resistin, and visfatin are adipokines that regulate reproductive events via the brain.

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.

scholarly journals 280.Reproductive consequences of circadian dysfunction: fertility in the Bmal1 null mouse

2004 ◽  
Vol 16 (9) ◽  
pp. 280 ◽  
Author(s):  
M. J. Boden ◽  
D. J. Kennaway
Keyword(s):  
Clock Genes ◽  
Reproductive Function ◽  
Blastocyst Stage ◽  
Null Mouse ◽  
Wild Type ◽  
Peripheral Tissues ◽  
Seminal Vesicle Weight ◽  
Natural Mating ◽  
Reproductive Consequences ◽  
The Brain

Circadian rhythms are generated by a suite of genes called clock genes that are expressed in the brain and also in many peripheral tissues. In the peripheral tissues, these genes assist in regulating the expression of many genes involved in cell growth, angiogenesis and development. Bmal1 is a critical gene involved in circadian rhythm generation. Here we report on the fertility and fecundity of Bmal1 knockout mice (Bmal1–/–). Male Bmal1–/– mice have impaired fertility compared to controls [(litters produced/number of animals) wild type (5/5), CBA controls (5/5), Bmal1–/– (1/15)]. Fifty percent of male Bmal1–/– mice had defective caudal sperm, showing sperm that was both non-motile and malformed. Seminal vesicle weight was significantly reduced in the Bmal1–/– mice (50% reduction) in males at both 4 and 5.5 months old. Female Bmal1–/– mice had irregular oestrus cycles and failed to maintain a pregnancy to term following natural mating [(litters produced/number of animals) wild type (5/5) CBA controls (5/5) Bmal1–/– (0/5)]. When embryos were flushed from the uterus 4 days after natural mating, there was a reduced number of released oocytes and a reduced development to blastocysts in the Bmal1–/– female mice. Following a standard PMSG/HCG super ovulation protocol, Bmal1–/– mice showed both a reduction in ovulation rate as well as a slowed progression of embryos to blastocyst stage (Table 1, see PDF file). These results suggest that disruption of a key clock gene has detrimental consequences on fertility in the mouse. Further, this reduction in fertility appears to be acting at multiple levels. Continued investigation into the importance of rhythm genes in reproductive function is required.

Serotonin effect on deiodinating activity in the rat

2003 ◽  
Vol 81 (7) ◽  
pp. 747-751 ◽  
Author(s):  
Alessio Sullo ◽  
Guglielmo Brizzi ◽  
Nicola Maffulli
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Cold Exposure ◽  
Type Ii ◽  
Indirect Measure ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
The Brain

Serotonin (5-HT) and thyroid hormones are part of a complex system modulating eating behaviour and energy expenditure. 5'-Deiodinase (5'-D) converts the relatively inactive thyroxine (T4) to triiodothyronine (T3), and its activity is an indirect measure of T3 production in peripheral tissues, particularly in the brain, intrascapular brown adipose tissue (IBAT), heart, liver, and kidney. We evaluated the effect of 5-HT on 5'-D activity during basal conditions and after short (30 min) cold exposure (thyroid stimulating hormone stimulation test, TST). 5'-D activity was assessed in the liver, heart, brain, kidney, and IBAT. TST increases 5'-D activity in the brain, heart, and IBAT and decreases it in kidney, leaving it unchanged in the liver. 5-HT alone did not modify 5'-D activity in the organs under study but decreased it in the IBAT, heart, and brain when injected before the TST was administered. Our results confirm the important role of 5-HT in thermoregulation, given its peripheral site of action, in modulating heat production controlling intracellular T3 production. These effects are more evident when heat production is upregulated during cold exposure in organs containing type II 5'-D, such as the brain, heart, and IBAT, which are able to modify their function during conditions that alter energy balance. In conclusion, 5-HT may also act peripherally directly on the thyroid and organs containing type II 5'-D, thus controlling energy expenditure through heat production.Key words: serotonin, deiodinase activity, thyroid hormone, brown adipose tissue, thermogenesis, rat organs.

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.

Gastric inhibitory polypeptide: a gut hormone with anabolic functions

1989 ◽  
Vol 2 (3) ◽  
pp. 169-174 ◽  
Author(s):  
B. Beck
Keyword(s):  
Adipose Tissue ◽  
Intestinal Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Metabolic Effects ◽  
Gastrointestinal Hormone ◽  
Peripheral Tissues ◽  
Gut Hormone ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
The Brain

Summary The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic β cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.

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 Role of GnRH Neurons and Their Neuronal Afferents as Key Integrators between Food Intake Regulatory Signals and the Control of Reproduction

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Juan Roa
Keyword(s):  
Food Intake ◽  
Metabolic Control ◽  
Reproductive Function ◽  
Energy Availability ◽  
Energy Status ◽  
Metabolic Factors ◽  
Metabolic Hormones ◽  
Reproductive Axis ◽  
Metabolic Information

Reproductive function is regulated by a plethora of signals that integrate physiological and environmental information. Among others, metabolic factors are key components of this circuit since they inform about the propitious timing for reproduction depending on energy availability. This information is processed mainly at the hypothalamus that, in turn, modulates gonadotropin release from the pituitary and, thereby, gonadal activity. Metabolic hormones, such as leptin, insulin, and ghrelin, act as indicators of the energy status and convey this information to the reproductive axis regulating its activity. In this review, we will analyse the central mechanisms involved in the integration of this metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of GnRH, Kiss1, NPY, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction.

scholarly journals Role of leptin in female reproduction

2015 ◽  
Vol 53 (1) ◽  
Author(s):  
Antonio Pérez-Pérez ◽  
Flora Sánchez-Jiménez ◽  
Julieta Maymó ◽  
José L. Dueñas ◽  
Cecilia Varone ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Reproductive Function ◽  
Fat Distribution ◽  
Female Reproduction ◽  
Cellular Mechanisms ◽  
Complex Interactions ◽  
Physiological Processes ◽  
Integral Role ◽  
The Brain

AbstractReproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

Adipose circadian clocks: coordination of metabolic rhythms by clock genes, steroid hormones, and PPARs

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Katherine C. Krueger ◽  
Brian J. Feldman
Keyword(s):  
Adipose Tissue ◽  
Hormone Receptors ◽  
Clock Genes ◽  
Feeding Activity ◽  
Feedback Regulation ◽  
Rhythmic Activity ◽  
Energy Status ◽  
Peripheral Tissues ◽  
Metabolic Gene Expression ◽  
Central Clock

AbstractA central clock consisting of interconnected positive and negative feedback gene loops operates in the brain, tying rhythmic activity to the 24-h day. The central clock entrains similar feedback loops present in most peripheral tissues to coordinate metabolic gene expression among organs and with feeding activity for more efficient utilization of resources. Recent studies are beginning to elucidate the intricate feedback mechanisms among central and peripheral clocks and their roles in activity and metabolic homeostasis. Adipose tissue serves as a major energy storage organ and releases paracrine and endocrine hormones to signal energy status to other organs. Within the adipose tissue, the transcriptional feedback regulation between clock genes and nuclear hormone receptors, together with direct protein associations among these molecules, ensures the expression of metabolic genes at the appropriate time. This review will summarize the important components and mechanisms of adipose clock entrainment, particularly highlighting instructive studies carried out in mice. This research not only illustrates the intricate connections between clocks and metabolism but also provides potential mechanisms to correct abnormalities induced by disrupted sleep or poor diet.

scholarly journals Adipokines and the Female Reproductive Tract

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Maxime Reverchon ◽  
Christelle Ramé ◽  
Michael Bertoldo ◽  
Joëlle Dupont
Keyword(s):  
Adipose Tissue ◽  
Reproductive Tract ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Female Reproductive Tract ◽  
Ovary Syndrome ◽  
Reproductive Axis ◽  
Endocrine Effect ◽  
Hypothalamic Pituitary Axis

It is well known that adipose tissue can influence puberty, sexual maturation, and fertility in different species. Adipose tissue secretes molecules called adipokines which most likely have an endocrine effect on reproductive function. It has been revealed over the last few years that adipokines are functionally implicated at all levels of the reproductive axis including the gonad and hypothalamic-pituitary axis. Many studies have shown the presence and the role of the adipokines and their receptors in the female reproductive tract of different species. These adipokines regulate ovarian steroidogenesis, oocyte maturation, and embryo development. They are also present in the uterus and placenta where they could create a favorable environment for embryonic implantation and play a key role in maternal-fetal metabolism communication and gestation. Reproductive functions are strongly dependent on energy balance, and thereby metabolic abnormalities can lead to the development of some pathophysiologies such as polycystic ovary syndrome (PCOS). Adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS.

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