The mechanisms mediating suppression of reproduction in response to decreased nutrient availability remain undefined, with studies suggesting regulation occurs within the hypothalamus, pituitary, or gonads. By manipulating glucose utilization and GLUT1 expression in a pituitary gonadotrope cell model and in primary gonadotropes, we show GLUT1-dependent stimulation of glycolysis, but not mitochondrial respiration, by the reproductive neuropeptide GnRH. GnRH stimulation increases gonadotrope GLUT1 expression and translocation to the extracellular membrane. Maximal secretion of the gonadotropin Luteinizing Hormone is supported by GLUT1 expression and activity, and GnRH-induced glycolysis is recapitulated in primary gonadotropes. GLUT1 expression increases in vivo during the GnRH-induced ovulatory LH surge and correlates with GnRHR. We conclude that the gonadotropes of the anterior pituitary sense glucose availability and integrate this status with input from the hypothalamus via GnRH receptor signaling to regulate reproductive hormone synthesis and secretion.
#1Richard B. McCosh(UCSD: University of California, San Diego)H-Index: 9
#2Michael J Kreisman(UCSD: University of California, San Diego)H-Index: 4
Last. Kellie M Breen(UCSD: University of California, San Diego)H-Index: 9
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Stress suppresses pulsatile luteinising hormone (LH) secretion in a variety of species, although the mechanism underlying this inhibition of reproductive function remains unclear. Metabolic stress, particularly hypoglycaemia, is a clinically-relevant stress type that is modelled with bolus insulin injection (insulin-induced hypoglycaemia). The present study utilised ovariectomised C57BL/6 mice to test the hypothesis that acute hypoglycaemia suppresses pulsatile LH secretion via central mechanism...
#1Taeshin Kim(UCSD: University of California, San Diego)H-Index: 7
#2Danmei Li(UCSD: University of California, San Diego)H-Index: 7
Last. Mark A. Lawson(UCSD: University of California, San Diego)H-Index: 25
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: A defining characteristic of the hypothalamus-pituitary-gonad reproductive endocrine axis is the episodic secretion of the pituitary gonadotropin hormones LH and FSH by the anterior pituitary gonadotropes. Hormone secretion is dictated by pulsatile stimulation, with GnRH released by hypothalamic neurons that bind and activate the G protein-coupled GnRH receptor expressed by gonadotropes. Hormone secretion and synthesis of gonadotropins are influenced by the amplitude and frequency of GnRH stim...
#1Tomohiro Terasaka(UCSD: University of California, San Diego)H-Index: 10
#2Taeshin Kim(UCSD: University of California, San Diego)H-Index: 7
Last. Mark A. Lawson(UCSD: University of California, San Diego)H-Index: 25
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: Gonadotropin secretion, which is elicited by GnRH stimulation of the anterior pituitary gonadotropes, is a critical feature of reproductive control and the maintenance of fertility. In addition, activation of the GnRH receptor (GnRHR) regulates transcription and translation of multiple factors that regulate the signaling response and synthesis of gonadotropins. GnRH stimulation results in a broad redistribution of mRNA between active and inactive polyribosomes within the cell, but the mechanis...
#2Yongchao Ge(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 28
Last. Stuart C. Sealfon(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 71
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Author(s): Ruf-Zamojski, Frederique; Ge, Yongchao; Pincas, Hanna; Shan, Jidong; Song, Yinghui; Hines, Nika; Kelley, Kevin; Montagna, Cristina; Nair, Pranav; Toufaily, Chirine; Bernard, Daniel J; Mellon, Pamela L; Nair, Venugopalan; Turgeon, Judith L; Sealfon, Stuart C | Abstract: LβT2 and αT3-1 are important, widely studied cell line models for the pituitary gonadotropes that were generated by targeted tumorigenesis in transgenic mice. LβT2 cells are more mature gonadotrope precursors than αT3-1...
#1Karen J. Tonsfeldt(UCSD: University of California, San Diego)H-Index: 9
#2Erica L. Schoeller(UCSD: University of California, San Diego)H-Index: 3
Last. Pamela L. Mellon(UCSD: University of California, San Diego)H-Index: 75
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: In rodents, the preovulatory LH surge is temporally gated, but the timing cue is unknown. Estrogen primes neurons in the anteroventral periventricular nucleus (AVPV) to secrete kisspeptin, which potently activates GnRH neurons to release GnRH, eliciting a surge of LH to induce ovulation. Deletion of the circadian clock gene Bmal1 results in infertility. Previous studies have found that Bmal1 knockout (KO) females do not display an LH surge at any time of day. We sought to determine whether neu...
#1Alona Feldman(Technion – Israel Institute of Technology)H-Index: 4
#2Ayah Saleh(Technion – Israel Institute of Technology)H-Index: 1
Last. Philippa Melamed(Technion – Israel Institute of Technology)H-Index: 21
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The connection between metabolism and reproductive function is well recognized, and we hypothesized that the pituitary gonadotropes, which produce luteinizing hormone and follicle-stimulating hormo...
: Transcription factors and signaling pathways that regulate stem cells and specialized hormone-producing cells in the pituitary gland have been the subject of intense study and have yielded a mechanistic understanding of pituitary organogenesis and disease. However, the regulation of stem cell proliferation and differentiation, the heterogeneity among specialized hormone-producing cells, and the role of nonendocrine cells in the gland remain important, unanswered questions. Recent advances in s...
: Gonadotropin-releasing hormone (GnRH) stimulation of its eponymous receptor on the surface of endocrine anterior pituitary gonadotrope cells (gonadotropes) initiates multiple signaling cascades that culminate in the secretion of luteinizing and follicle-stimulating hormones, which have critical roles in fertility and reproduction. Enhanced luteinizing hormone biosynthesis, a necessary event for ovulation, requires a signaling pathway characterized by calcium influx through L-type calcium chann...
#2Miguel Fribourg(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 13
Last. Stuart C. Sealfon(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 71
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The LβT2 mouse pituitary cell line has many characteristics of a mature gonadotrope and is a widely used model system for studying developmental processes and the response to gonadotropin-releasing hormone (GnRH). The global epigenetic landscape, which contributes to cell-specific gene regulatory mechanisms, and the single-cell transcriptome response variation of LβT2 cells have not been previously investigated. Here, we integrate the transcriptome and genome-wide chromatin accessibility state o...
#1Song Li(UCSD: University of California, San Diego)H-Index: 2
#2Ekaette F. Mbong(UCSD: University of California, San Diego)H-Index: 4
Last. Mark A. Lawson(UCSD: University of California, San Diego)H-Index: 25
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: An emerging body of evidence supports the concept that the pituitary is a site for integration of multiple physiological and metabolic signals that inform and modulate endocrine pathways. Multiple endocrine mediators of energy balance and adiposity are known to impinge on the neuroendocrine axis regulating reproduction. Observations in humans show that obesity is correlated with decreased gonadotropin secretion, and studies have also suggested that pituitary sensitivity to stimulation by gonad...