Gwen V Childs

Gwen V Childs
University of Arkansas for Medical Sciences | UAMS · Department of Neurobiology and Developmental Sciences

Ph.D.

About

271
Publications
38,499
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Introduction
We are currently studying the role of leptin in the regulation of the pituitary, including mechanisms behind its support of cells that secrete growth hormone or gonadotropins. Our latest focus is on the paracrine role of leptin produced in the pituitary itself, comparing the importance of pituitary leptin to that from adipocytes. We use selective knockouts to study leptin interactions with pituitary cells. We discovered that leptin is required for somatotropes to maintain body composition.
Additional affiliations
April 2000 - present
University of Arkansas for Medical Sciences
Position
  • Research: University of Arkansas for Medical Sciences
Description
  • Studying leptin interactions with pituitary somatotropes, and gonadotropes
January 2000 - December 2013
January 1989 - January 1992
Baylor College of Medicine
Position
  • Professor (Associate)
Education
September 1968 - June 1972
University of Iowa
Field of study
  • Anatomy: Neuroendocrinology
September 1966 - June 1968
University of Rochester
Field of study
  • Biophysics and Education
September 1962 - June 1966
Whitman College
Field of study
  • Biology

Publications

Publications (271)
Article
Full-text available
Leptin regulates food intake and energy expenditure and is produced in adipocytes, the pituitary, and several other tissues. Animals that are leptin or leptin receptor deficient have major metabolic complications, including obesity. This study tests the hypothesis that the pituitary somatotrope may contribute a source of leptin that maintains some...
Article
Full-text available
Pituitary somatotropes perform the key function of coordinating organismic growth and body composition with metabolic signals. However, the mechanism by which they sense and respond to metabolic signals via the adipokine leptin is unknown. The complex interplay between the heterogeneous cell types of the pituitary confounds identification of somato...
Article
Full-text available
Leptin receptor (LEPR) signaling controls appetite and energy expenditure. Somatotrope-specific deletion of the LEPRb signaling isoform causes growth hormone deficiency (GHD) and obesity. The present study selectively ablated Lepr exon 1 in somatotropes, which removes the signal peptide, causing the loss of all isoforms of LEPR. Excision of Lepr ex...
Article
Full-text available
The adipokine, leptin, is a hormonal gateway, signaling energy stores to appetite-regulatory neurons, permitting reproduction when stores are sufficient. Dual-labeling for leptin receptors (LEPR) and gonadotropins or growth hormone (GH) revealed a 2-fold increase in LEPR during proestrus, some of which was seen in luteinizing hormone (LH) gonadotro...
Article
Full-text available
Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and the pituitary gland among other tissues. Best known for its role in regulating appetite and energy expenditure, leptin is produced largely by and in proportion to white fat cells. Leptin is also important to the maintenance and function of the GH cells of the pitui...
Article
OBJECTIVES/GOALS: Maternal undernutrition, a form of malnutrition, can alter neonatal leptin signaling and result in metabolic dysfunction in adulthood. We developed a mild undernutrition model to relate more to societys nutritional challenges and to test the hypothesis that a shift in the neonatal leptin surge would result in sex-specific metaboli...
Chapter
Full-text available
Pituitary cell function is impacted by metabolic states and therefore must receive signals that inform them about nutritional status or adiposity. A primary signal from adipocytes is leptin, which recent studies have shown regulates most pituitary cell types. Subsets of all pituitary cell types express leptin receptors and leptin has been shown to...
Article
Full-text available
To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetical...
Article
Full-text available
The cyclic expression of gonadotropin releasing-hormone receptors (GnRHR), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by pituitary gonadotropes is critical in the female reproductive process. We have shown that the translational regulator Musashi (MSI) binds to Gnrhr mRNA and inhibits its translation, and the gonadotrope-speci...
Article
Full-text available
Malnutrition alters leptin signaling, resulting in dysregulation of pituitary somatotropes that may be sex-specific. We reported sex differences in acute fasting responses with reductions in serum leptin in males, but not females (1). Maternal undernutrition can also alter the neonatal leptin surge by blunting with 50% food deprivation (2), causing...
Article
Full-text available
The Musashi RNA-binding protein functions as a gatekeeper of cell maturation and plasticity through the control of target mRNA translation. It is understood that Musashi promotes stem cell self-renewal and opposes differentiation. While Musashi is best characterized as a repressor of target mRNA translation, we have shown that Musashi can activate...
Article
Full-text available
The pituitary gland is the major endocrine organ that produces and secretes hormones in response to hypothalamic signals to regulate important processes like growth, reproduction, and stress. The anterior pituitary adapts to metabolic and reproductive needs by exhibiting cellular plasticity, resulting in altered hormone production and secretion. Th...
Article
Full-text available
The proper expression of gonadotropin-releasing hormone receptors (GnRHRs) by pituitary gonadotropes is critical for maintaining maximum reproductive capacity. GnRH receptor expression must be tightly regulated in order to maintain the normal pattern of expression through the estrous cycle in rodents, which is believed to be important for interpret...
Article
Full-text available
Alzheimer's disease (AD) is associated with disturbances in blood glucose regulation, and type-2 diabetes elevates the risk for dementia. A role for amyloid-β peptide (Aβ) in linking these age-related conditions has been proposed, tested primarily in transgenic mouse lines that overexpress mutated amyloid precursor protein (APP). Because APP has it...
Article
Full-text available
The adipokine leptin regulates energy homeostasis through ubiquitously expressed leptin receptors. Leptin has a number of major signaling targets in the brain, including cells of the anterior pituitary (AP). We have previously reported that mice lacking leptin receptors in AP somatotropes display growth hormone (GH) deficiency, metabolic dysfunctio...
Article
Anterior pituitary somatotropes are important metabolic sensors responding to leptin by secreting growth hormone (GH). However, reduced leptin signals caused by fasting have not always correlated with reduced serum GH. Reports show that fasting may stimulate or reduce GH secretion, depending on the species. Mechanisms underlying these distinct soma...
Article
A healthy nutritional state is required for all aspects of reproduction and signaled by the adipokine leptin. Leptin acts in a relatively narrow concentration range; too much or too little will compromise fertility. The leptin signal timing is important to prepubertal development in both sexes. In the brain, leptin acts on ventral premammillary (PM...
Article
Full-text available
The mechanisms that mediate plasticity in pituitary function have long been a subject of vigorous investigation. Early studies overcame technical barriers and challenged conceptual barriers to identify multipotential and multihormonal cell populations that contribute to diverse pituitary stress responses. Decades of intensive study have challenged...
Preprint
Full-text available
The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigeneti...
Article
Full-text available
In normal individuals, pituitary somatotropes optimize body composition by responding to metabolic signals from leptin. To identify mechanisms behind leptin regulation of somatotropes, we used Cre‐LoxP technology to delete leptin receptors (LEPR) selectively in somatotropes and developed FACS‐purified populations containing 99% somatotropes. FACS‐p...
Article
Full-text available
Sufficient nutrition is critical for reproduction. We have previously shown that leptin, a circulating indicator of fat stores, signals to pituitary gonadotropes to maintain gonadotropin releasing hormone receptor (GnRHR) protein levels in female mice. We hypothesized that this process is post-transcriptional, happening primarily through regulation...
Article
Full-text available
The pituitary gland is a critical regulator of the neuroendocrine system. To further our understanding of the classification, cellular heterogeneity, and regulatory landscape of pituitary cell types, we performed and computationally integrated single cell (SC)/single nucleus (SN) resolution experiments capturing RNA expression, chromatin accessibil...
Article
Full-text available
The activation of transcription factor Pou1f1 at embryonic day 13 gives rise to the pituitary populations of somatotropes, lactotropes, and thyrotropes and these populations maintain expression of Pou1f1 throughout life. The Musashi family of RNA regulatory proteins is known to regulate stem cell fate by repressing translation of target mRNAs neede...
Article
Full-text available
Malnutrition causes dysregulated pituitary function, which may in part be due to lowered leptin signals. We showed that loss of somatotrope leptin receptors in mice reduces growth hormone (GH) secretion and promotes metabolic dysfunction in adults. More recently, we showed that adult male mice fasted for 12 or 24 hours also had significantly lowere...
Article
The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain larg...
Article
Full-text available
The Musashi family of mRNA translational regulators control both physiological and pathological stem cell self-renewal primarily by repressing target mRNAs that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish...
Article
Polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility, is associated with a breakdown in signaling within the hormone sensitive neural network that regulates gonadotropin-releasing hormone (GnRH) neurons, ultimately increasing GnRH neural output. Circuitry between GABAergic neurons in the arcuate nucleus (ARN) and GnRH n...
Article
Metabolic and reproductive demands are met and coordinated through the complex control of hormone synthesis and secretion exerted by the anterior pituitary. While pituitary cells are known to possess remarkable plasticity to change their cell fate and alter hormone production in response to ever changing environmental cues, the underlying molecular...
Article
Fasting results in a well-established rise in serum growth hormone (GH) in mice and humans. In mice, this coincides with increases in Gh and growth hormone releasing hormone receptor (Ghrhr) mRNA, as well as serum ghrelin. However, fasting also results in a dramatic decline in serum leptin and we have shown that pituitary somatotropes are dependent...
Article
Leptin is a critical mediator of metabolic regulation of the hypothalamic-pituitary gonadal (HPG) axis. We have previously shown that leptin is responsible for the optimal expression of GnRHR, a rate-limiting component of the reproductive process. Female mice lacking leptin receptors (Lepr-null) specifically on gonadotropes are sub-fertile. Their r...
Article
The developing pituitary is a rapidly changing environment that is constantly meeting the physiological demands of the growing organism. During early postnatal development, the anterior pituitary is refining patterns of anterior hormone secretion in response to numerous genetic factors. Our lab previously developed a somatotrope leptin receptor (LE...
Poster
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This poster displays preliminary data from our studies following our Gonadotrope-Lepr-null female mice through the estrous cycle to determine what role leptin plays in regulating gonadotrope functions.
Article
Full-text available
The adipokine leptin signals the body’s nutritional status to the brain, and particularly, the hypothalamus. However, leptin receptors (LEPRs) can be found all throughout the body and brain, including the pituitary. It is known that leptin is permissive for reproduction, and mice that cannot produce leptin (Lep/Lep) are infertile. Many studies have...
Article
Full-text available
The cyclic expression of pituitary gonadotropin-releasing hormone receptors (GnRHRs) may be an important checkpoint for leptin regulatory signals. Gonadotrope Lepr-null mice have reduced GnRHR levels, suggesting these receptors may be leptin targets. To determine if leptin stimulated GnRHRs directly, primary pituitary cultures or pieces were expose...
Article
Full-text available
The Musashi family of RNA binding proteins act to promote stem cell self-renewal and oppose cell differentiation predominantly through translational repression of mRNAs encoding pro-differentiation factors and inhibitors of cell cycle progression. During tissue development and repair however, Musashi repressor function must be dynamically regulated...
Poster
Full-text available
Leptin signaling to anterior pituitary somatotropes is required to maintain their function and to prevent Growth Hormone Deficiency (GHD). In order to determine the mechanisms by which leptin signaling regulates somatotrope function, we added a floxed tdTomato-eGFP Cre-reporter transgene to lines bearing Cre-recombinase driven by the rGH promoter a...
Conference Paper
Full-text available
The purification of somatotropes is vital for studies of molecular signaling pathways regulating growth hormone (GH). Successful purification approaches have depended on the production of GH protein stores,(1-3) or functional receptors for Growth hormone releasing hormone (GHRHR).(4) We recently developed a GH-deficient mouse model in which leptin...
Chapter
Full-text available
Immunohistochemistry began over 120 years ago when Von Behring discovered serum antibodies in 1890 and used them to cure diphtheria and tetanus. The precipitin test, developed by Dr. Kraus in 1897, demonstrated that these antitoxins reacted with antigens. In 1923, Dr. Michael Heidelberger quantified this reaction with the use of dyes attached to an...
Conference Paper
Full-text available
Leptin, an appetite-suppressing hormone produced largely by white fat cells, signals energy stores to the brain via receptors in the hypothalamus and is produced in several extra-adipocyte tissues, including the brain and the pituitary gland (1). By deleting the long-form of leptin receptor on somatotropes, we demonstrated that the leptin signal op...
Conference Paper
Full-text available
SUN-0653 Leptin, an important regulator of appetite and metabolism, is also permissive for fertility. Its importance to gonadotrope function was seen when selective loss of the JAK binding site of LEPR (exon 17) in gonadotropes impaired fertility in females.(1) Continuing studies focus on cellular mechanisms underlying the reproductive deficits. Mo...
Conference Paper
Full-text available
Leptin is a circulating hormone produced by white fat cells, the pituitary, and several other tissues that is best known for its role in appetite and energy regulation. Mice exhibit a surge in circulating leptin occurring between postnatal days (PND) 7-10 that decreases to adult leptin levels before the onset of puberty. This surge occurs independe...
Conference Paper
Full-text available
Students at UAMS have traditionally studied histology with microscopes and the computer program, Histology Time, that encouraged independent study, but limited faculty-student interactions. A major curriculum reconstruction offered the faculty an opportunity to convert most lecture and laboratory periods to interactive learning laboratories. Studen...
Article
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Deletion of the signaling domain of leptin receptors selectively in somatotropes, with Cre-loxP technology, reduced the percentage of immunolabeled GH cells and serum GH. We hypothesized that the deficit occurred when leptin's postnatal surge failed to stimulate an expansion in the cell population. To learn more about the deficiency in GH cells, we...
Article
Full-text available
Mice with somatotrope-specific deletion of the Janus kinase binding site in leptin receptors are GH deficient as young adults and become obese by 6 months of age. This study focused on the metabolic status of young (3-4.5 month old) preobese mutant mice. These mutants had normal body weights, lean body mass, serum leptin, glucose, and triglycerides...
Conference Paper
Full-text available
Thought to primarily be an adipokine, leptin is known to regulate appetite and energy expenditure via receptors in the hypothalamus. However, researchers now report extra-adipocyte sources of leptin with the potential for additional functions such as paracrine or developmental regulation. One of these sources is the pituitary somatotrope and, in or...
Conference Paper
Full-text available
Deletion mutant mice without leptin receptors on somatotrpoes (GH cells) have fewer immunolabeled GH cells. This study determined if stimulation will restore GH cells, in vitro. Freshly dissociated pituitaries from male mice were stimulated for 3 h with 0.1-30 nM Growth hormone releasing hormone (GHRH) either alone or with ghrelin (10nM). Media wer...
Article
Background: Associations of inflammation with occurrence of pain and paralysis in shingles have been well documented. Thus, the anti-inflammatory effect of acupuncture might improve or hasten pain relief and motor recovery in patients with shingles-associated pain and paralysis. Objective: To describe the possible role of acupuncture in motor defic...
Conference Paper
Full-text available
Leptin signals are important to the maintenance of somatotrope functions. When exon 17 of the leptin receptor gene is deleted selectively in somatotropes by Cre-loxP technology, mice express lower serum and pituitary levels of growth hormone (GH) and develop adult onset obesity by 6 months of age (Childs et al, 2011). In order to determine factors...
Article
Full-text available
Leptin, a potent anorexigenic hormone secreted primarily by adipocytes, is known to be expressed in the anterior pituitary. Studies in our laboratory found leptin proteins and mRNA predominantly in somatotropes in normal male and cycling female rats. In contrast, leptin expression predominated in gonadotropes during pregnancy and lactation. Leptin...