scholarly journals Liver receptor homologue-1 regulates gonadotrope function

2007 ◽  
Vol 38 (2) ◽  
pp. 207-219 ◽  
Author(s):  
Weiming Zheng ◽  
Jingying Yang ◽  
Qiaorong Jiang ◽  
Zhibin He ◽  
Lisa M Halvorson

Over the past decade, substantial advances have been made in our understanding of the transcription factors which regulate gene expression in gonadotropes. One of the most important of these factors, steroidogenic factor-1 (SF-1; NR5A1) is critical for gonadotropin and GnRH-receptor expression. Interestingly, a closely related nuclear hormone receptor, liver receptor homologue-1 (LRH-1; NR5A2) has recently been detected in the anterior pituitary gland; however, its functional significance in this tissue has not been investigated. For the experiments reported here, we hypothesized that LRH-1 plays a previously unrecognized role in gonadotrope physiology. Towards this end, we first demonstrate LRH-1 mRNA and protein expression in both primary pituitary cells and gonadotrope-derived cell lines. We next show that LRH-1 stimulates promoter activity of the GnRH-receptor and gonadotropin subunit genes. Within the LHβ gene, this response appears to be mediated by DNA-binding and transactivation through previously characterized SF-1 cis-elements. To our knowledge, this is the first report demonstrating a functional role for LRH-1 in the gonadotrope population of the anterior pituitary gland.

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5452-5466 ◽  
Author(s):  
Alex Reichenbach ◽  
Frederik J. Steyn ◽  
Mark W. Sleeman ◽  
Zane B. Andrews

Abstract Ghrelin is the endogenous ligand for the GH secretagogue receptor (GHSR) and robustly stimulates GH release from the anterior pituitary gland. Ghrelin also regulates the secretion of anterior pituitary hormones including TSH, LH, prolactin (PRL), and ACTH. However, the relative contribution of a direct action at the GHSR in the anterior pituitary gland vs. an indirect action at the GHSR in the hypothalamus remains undefined. We used a novel GHSR-enhanced green fluorescent protein (eGFP) reporter mouse to quantify GHSR coexpression with GH, TSH, LH, PRL, and ACTH anterior pituitary cells in males vs. females and in chow-fed or calorie-restricted (CR) mice. GHSR-eGFP-expressing cells were only observed in anterior pituitary. The number of GHSR-eGFP-expressing cells was higher in male compared with females, and CR did not affect the GHSR-eGFP cell number. Double staining revealed 77% of somatotrophs expressed GHSR-eGFP in both males and females. Nineteen percent and 12.6% of corticotrophs, 21% and 9% of lactotrophs, 18% and 19% of gonadotrophs, and 3% and 9% of males and females, respectively, expressed GHSR-eGFP. CR increased the number of TSH cells, but suppressed the number of lactotrophs and gonadotrophs, expressing GHSR-eGFP compared with controls. These studies support a robust stimulatory action of ghrelin via the GHSR on GH secretion and identify a previously unknown sexual dimorphism in the GHSR expression in the anterior pituitary. CR affects GHSR-eGFP expression on lactotrophs, gonadotrophs, and thyrotrophs, which may mediate reproductive function and energy metabolism during periods of negative energy balance. The low to moderate expression of GHSR-eGFP suggests that ghrelin plays a minor direct role on remaining anterior pituitary cells.


2016 ◽  
Vol 35 (4) ◽  
pp. 463-475 ◽  
Author(s):  
Sonia A. Ronchetti ◽  
María S. Bianchi ◽  
Beatriz H. Duvilanski ◽  
Jimena P. Cabilla

Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status.


1972 ◽  
Vol 20 (1) ◽  
pp. 1-12 ◽  
Author(s):  
GEORGES PELLETIER ◽  
ALEX B. NOVIKOFF

All five known secretory cell types of the rat anterior pituitary gland display nucleoside diphosphatase (NDPase) activity throughout the endoplasmic reticulum (ER), including the nuclear envelope but not the specialized region of ER at the inner aspect of the Golgi apparatus known as GERL. The functions of the ER diphosphatase are currently unknown. However, speculations concerning its association with glucuronyl transferase may focus on the metabolic roles of the ER in pituitary cells other than those directly related to secretory protein transport. The gonadotrophs have been studied for thiamine pyrophosphatase and acid phosphatase activities as well as NDPase activity. The results suggest that the secretory granules of gonadotrophs arise from GERL and not from the inner element of the Golgi apparatus. The innermost Golgi element of this cell type shows NDPase and thiamine pyrophosphatase activities and appears to be composed, in part at least, of anastomosing tubules. Nucleoside phosphatase activity is also present at the surfaces of all five secretory cell types and between the cells and adjacent blood capillaries.


Endocrine ◽  
1997 ◽  
Vol 6 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Adele M. Turzillo ◽  
Christine Campion Quirk ◽  
Jennifer L. Juengel ◽  
Terry M. Nett ◽  
Colin M. Clay

2008 ◽  
Vol 108 (3-4) ◽  
pp. 345-355 ◽  
Author(s):  
Magdalena Ciechanowska ◽  
Magdalena Łapot ◽  
Tadeusz Malewski ◽  
Krystyna Mateusiak ◽  
Tomasz Misztal ◽  
...  

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 859-864 ◽  
Author(s):  
Meghan M. Taylor ◽  
Sara L. Bagley ◽  
Willis K. Samson

Intermedin (IMD), a novel member of the adrenomedullin (AM), calcitonin gene-related peptide (CGRP), amylin (AMY) peptide family, has been reported to act promiscuously at all the known receptors for these peptides. Like AM and CGRP, IMD acts in the circulation to decrease blood pressure and in the brain to inhibit food intake, effects that could be explained by activation of the known CGRP, AM, or AMY receptors. Because AM, CGRP, and AMY have been reported to affect hormone secretion from the anterior pituitary gland, we examined the effects of IMD on GH, ACTH, and prolactin secretion from dispersed anterior pituitary cells harvested from adult male rats. IMD, in log molar concentrations ranging from 1.0 pm to 100 nm, failed to significantly alter basal release of the three hormones. Similarly, IMD failed to significantly alter CRH-stimulated ACTH or TRH-stimulated prolactin secretion in vitro. However, IMD concentration-dependently inhibited GHRH-stimulated GH release from these cell cultures. The effects of IMD, although requiring higher concentrations, were as efficacious as those of somatostatin and, like somatostatin, may be mediated, at least in part, by decreasing cAMP accumulation. These actions of IMD were not shared by other members of the AM-CGRP-AMY family of peptides, suggesting the presence of a novel, unique IMD receptor in the anterior pituitary gland and a potential neuroendocrine action of IMD to interact with the hypothalamic mechanisms controlling growth and metabolism.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 308-319 ◽  
Author(s):  
Laura E. Ellestad ◽  
Tom E. Porter

Glucocorticoids play a role in functional differentiation of pituitary somatotrophs and lactotrophs during embryogenesis. Ras-dva was identified as a gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic stem cells-1, a transcription factor known to be critical in pituitary development, and has an expression profile in the chicken embryonic pituitary gland that is consistent with in vivo regulation by glucocorticoids. The objective of this study was to characterize expression and regulation of ras-dva mRNA in the developing chicken anterior pituitary. Pituitary ras-dva mRNA levels increased during embryogenesis to a maximum on embryonic day (e) 18 and then decreased and remained low or undetectable after hatch. Ras-dva expression was highly enriched in the pituitary gland on e18 relative to other tissues examined. Glucocorticoid treatment of pituitary cells from mid- and late-stage embryos rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional target of glucocorticoids. A reporter construct driven by 4 kb of the chicken ras-dva 5′-flanking region, containing six putative pituitary-specific transcription factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR) binding sites, was highly activated in embryonic pituitary cells and up-regulated by corticosterone. Mutagenesis of the most proximal Pit-1 site decreased promoter activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit-1. However, mutating putative GR binding sites did not substantially reduce induction of ras-dva promoter activity by corticosterone, suggesting additional DNA elements within the 5′-flanking region are responsible for glucocorticoid regulation. We have identified ras-dva as a glucocorticoid-regulated gene that is likely expressed in cells of the Pit-1 lineage within the developing anterior pituitary gland.


2009 ◽  
Vol 204 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Kotaro Horiguchi ◽  
Motoshi Kikuchi ◽  
Kenji Kusumoto ◽  
Ken Fujiwara ◽  
Tom Kouki ◽  
...  

Folliculo-stellate (FS) cells in the anterior pituitary gland appear to possess multifunctional properties. Recently, the development of transgenic rats (S100b–green fluorescent protein (GFP) rats) that express GFP specifically in FS cells in the anterior pituitary gland has allowed us to distinguish and observe living FS cells in other kinds of pituitary cells. We used S100b–GFP rats to investigate the topographic affinity of FS cells for other pituitary cells. We observed living FS cells in enzymatically dispersed anterior pituitary cells of S100b–GFP rats under a fluorescent microscope, and noted that FS cells markedly extended and contracted cytoplasmic processes and formed interconnections with neighboring FS cells. In addition, FS cells adhered to small clusters of GFP-negative cells, which were primarily hormone-producing cells, and these clusters further aggregated during the course of cytoplasmic contraction. In the presence of laminin, fibronectin, and varying types of collagen, FS cells showed marked changes in shape and specific proliferative activity; however, GFP-negative cells did not. On reverse transcription-PCR analysis and immunohistochemistry, FS cells were shown to express integrin subunits, which are the cell surface receptors for extracellular matrix (ECM). In the anterior pituitary gland, FS cells and the various types of hormone-producing cells generate a unique topography in the presence of basement membrane components and interstitial collagens. The novel characteristics of FS cells observed in the present study suggest that in the anterior pituitary gland, FS cells play important roles in determining and/or maintaining local cellular arrangement in the presence of ECM components.


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