scholarly journals IGF-I regulates pro-opiomelanocortin and GH gene expression in the mouse pituitary gland

2003 ◽  
Vol 178 (1) ◽  
pp. 71-82 ◽  
Author(s):  
J Honda ◽  
Y Manabe ◽  
R Matsumura ◽  
S Takeuchi ◽  
S Takahashi
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Northern Blotting ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Gh Receptor ◽  
Pomc Mrna ◽  
Igf I ◽  
Mouse Pituitary

IGF-I is expressed in somatotrophs, and IGF-I receptors are expressed in most somatotrophs and some corticotrophs in the mouse pituitary gland. Our recent study demonstrated that IGF-I stimulates the proliferation of corticotrophs in the mouse pituitary. These results suggested that somatotrophs regulate corticotrophic functions as well as somatotrophic functions by the mediation of IGF-I molecules. The present study aimed to clarify factors regulating pituitary IGF-I expression and also the roles exerted by IGF-I within the mouse anterior pituitary gland. Mouse anterior pituitary cells were isolated and cultured under serum-free conditions. GH (0.5 or 1 microg/ml), ACTH (10(-8) or 10(-7) M), GH-releasing hormone (GHRH; 10(-8) or 10(-7) M), dexamethasone (DEX; 10(-8) or 10(-7) M) and estradiol-17beta (e2; 10(-11) or 10(-9) M) were given for 24 h. IGF-I mRNA levels were measured using competitive RT-PCR, and GH and pro-opiomelanocortin (POMC) mRNA levels were measured using Northern blotting analysis. GH treatment significantly increased IGF-I mRNA levels (1.5- or 2.1-fold). ACTH treatment did not alter GH and IGF-I mRNA levels. IGF-I treatment decreased GH mRNA levels (0.7- or 0.5-fold), but increased POMC mRNA levels (1.8-fold). GH treatment (4 or 8 microg/ml) for 4 days increased POMC mRNA levels. GHRH treatment increased GH mRNA levels (1.3-fold), but not IGF-I mRNA levels. DEX treatment significantly decreased IGF-I mRNA levels (0.8-fold). e2 treatment did not affect IGF-I mRNA levels. GH receptor mRNA, probably with GH-binding protein mRNA, was detected in somatotrophs, and some mammotrophs and gonadotrophs by in situ hybridization using GH receptor cDNA as a probe. These results suggested that IGF-I expression in somatotrophs is regulated by pituitary GH, and that IGF-I suppresses GH expression and stimulates POMC expression at the transcription level. Pituitary IGF-I produced in somatotrophs is probably involved in the regulation of somatotroph and corticotroph functions.

scholarly journals Reporter Expression, Induced by a Growth Hormone Promoter-Driven Cre Recombinase (rGHp-Cre) Transgene, Questions the Developmental Relationship between Somatotropes and Lactotropes in the Adult Mouse Pituitary Gland

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 1946-1953 ◽  
Author(s):  
Raul M. Luque ◽  
Geraldine Amargo ◽  
Shinya Ishii ◽  
Corrinne Lobe ◽  
Roberta Franks ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Transgenic Mouse ◽  
Anterior Pituitary ◽  
Adult Mouse ◽  
Small Subset ◽  
Parental Line ◽  
Pituitary Cells ◽  
Placental Alkaline Phosphatase ◽  
Developmental Studies ◽  
Mouse Pituitary

This report describes the development and validation of the rGHp-Cre transgenic mouse that allows for selective Cre-mediated recombination of loxP-modified alleles in the GH-producing cells of the anterior pituitary. Initial screening of the rGHp-Cre parental line showed Cre mRNA was specifically expressed in the anterior pituitary gland of adult Cre+/− mice and cephalic extracts of e17 Cre+/− fetuses. Heterozygote rGHp-Cre transgenic mice were crossbred with Z/AP reporter mice to generate Cre+/−,Z/AP+/− offspring. In this model system, the GH promoter-driven, Cre-mediated recombination of the Z/AP reporter leads to human placental alkaline phosphatase (hPLAP) expression that serves to mark cells that currently produce GH, in addition to cells that would have differentiated from GH cells but currently do not express the GH gene. Double immunocytochemistry of adult male and female Cre+/−,Z/AP+/− pituitary cells revealed the majority (∼99%) of GH-producing cells of the anterior pituitary also expressed hPLAP, whereas ACTH-, TSH-, and LH-producing cells were negative for hPLAP, confirming previous reports that corticotropes, thyrotropes, and gonadotropes develop independently of the somatotrope lineage. A small subset (∼10%) of the prolactin-producing cells was positive for hPLAP, consistent with previous reports showing lactotropes can arise from somatotropes during pituitary development. However, the fact that 90% of prolactin-producing cells were negative for hPLAP suggests that the majority of lactotropes in the adult mouse pituitary gland develop independently of the somatotrope lineage. In addition to developmental studies, the rGHp-Cre transgenic mouse will provide a versatile tool to study the role of a variety of genes in somatotrope function and neoplastic transformation.

Effects of vasopressin and elimination of corticotropin-releasing hormone-target cells on pro-opiomelanocortin mRNA levels and adrenocorticotropin secretion in ovine anterior pituitary cells

1997 ◽  
Vol 154 (1) ◽  
pp. 139-147 ◽  
Author(s):  
S A van de Pavert ◽  
I J Clarke ◽  
A Rao ◽  
K E Vrana ◽  
J Schwartz
Keyword(s):  
Protein Kinase C ◽  
Steady State ◽  
Anterior Pituitary ◽  
Target Cells ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Acth Secretion ◽  
Kinase C ◽  
Pomc Mrna ◽  
Anterior Pituitary Cells

Abstract Although arginine-vasopressin (AVP) is reported to produce greater ACTH biosynthetic and secretory responses than does corticotropin-releasing hormone (CRH) in sheep anterior pituitary cells, neither factor appears to increase pro-opiomelanocortin (POMC) mRNA levels, as does CRH in the cells of some other species. Since only a fraction of cells that express POMC mRNA may be able to respond to AVP, the aim of this study was to further delineate the regulation of POMC mRNA in ovine anterior pituitary corticotrophs, as a whole and in functional subpopulations of corticotrophs. We measured the effects of AVP, CRH or activation of protein kinase C by phorbol myristate acetate (PMA) in cultured cells. We compared responses in intact populations with those of cultures from which CRH-target cells were pharmacologically eliminated. Dissociated adult ovine anterior pituitary cells were cultured overnight, treated with either vehicle (intact) or a CRH-toxin conjugate that specifically eliminates CRH-target cells (CRH-target-depleted), washed, returned to culture and subsequently challenged with vehicle, AVP (100 nm), CRH (10 nm) or PMA (1 μm) for 5 h. The media were assayed for ACTH by RIA and the cells for POMC mRNA by Northern blot analysis. In intact populations, AVP and CRH increased ACTH secretion from 6·5 ±1·2 to 216 ±22 and 81 ± 14 ng/well respectively, but only AVP caused an increase in steady-state POMC mRNA levels (+48 ± 10%). Direct activation of protein kinase C with PMA mimicked the effect of AVP on ACTH secretion (318 ± 16 ng/well), but did not alter POMC mRNA levels. In CRH-target-depleted populations, control ACTH secretion (11 ± 3 ng/well) and POMC mRNA (+69 ±7%) were elevated, compared with intact populations. AVP (55 ± 8 ng/well) and PMA (120 ± 17 ng/well), but not CRH, increased ACTH secretion; POMC mRNA was not significantly elevated by any of the treatments. Taken together, these data provide further support for the notion of dissociation between secretion of ACTH and expression of POMC mRNA, and demonstrate that AVP increases steady-state POMC mRNA levels in ovine anterior pituitary cells. The data are also consistent with the concept that complex interactions, possibly including those between cells, influence ACTH secretion and steady-state POMC mRNA levels. Journal of Endocrinology (1997) 154, 139–147

scholarly journals Ras-dva Is a Novel Pit-1- and Glucocorticoid-Regulated Gene in the Embryonic Anterior Pituitary Gland

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 308-319 ◽  
Author(s):  
Laura E. Ellestad ◽  
Tom E. Porter
Keyword(s):  
Transcription Factor ◽  
Pituitary Gland ◽  
Binding Sites ◽  
Anterior Pituitary ◽  
Promoter Activity ◽  
Embryonic Stem ◽  
Anterior Pituitary Gland ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Flanking Region

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.

scholarly journals Cocaine- and Amphetamine-Regulated Transcript Is Localized in Pituitary Lactotropes and Is Regulated during Lactation

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1213-1223 ◽  
Author(s):  
Sean M. Smith ◽  
Joan M. Vaughan ◽  
Cynthia J. Donaldson ◽  
Rosette E. Fernandez ◽  
Chien Li ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Mrna Expression ◽  
Anterior Pituitary ◽  
Cellular Localization ◽  
Supraoptic Nucleus ◽  
Protein Release ◽  
Female Rats ◽  
Dopamine Receptor Agonist ◽  
Pituitary Cells ◽  
Mrna Levels

Cocaine- and amphetamine-regulated transcript (CART) is a highly expressed peptide implicated in the regulation of feeding, reward and reinforcement, and stress-related behaviors. CART has been localized to discrete cell populations in the brain, gut, adrenal gland, and pancreas. In contrast, CART-producing cell types in the pituitary gland remain ill defined. In the present study, double-label immunohistochemistry, employing a high-affinity antiserum we generated against CART-(62–102), was used to identify CART-producing cells in the pituitary gland. In the anterior pituitary, the majority of CART immunoreactivity (-ir) was localized in lactotropes; minor populations of CART-ir cells were identified as somatotropes and corticotropes. In the posterior pituitary, CART-ir extensively colocalized with oxytocin-containing fibers; in contrast, only a few vasopressin fibers contained CART-ir. As expected, CART colocalized with oxytocin in magnocellular neurons of the supraoptic nucleus. The effects of bromocriptine, a potent dopamine receptor agonist, were examined to determine whether CART mRNA expression and protein release are regulated in a similar fashion as prolactin. Similar to prolactin, CART mRNA expression and protein release were significantly decreased after bromocriptine treatment of dispersed rat anterior pituitary cells in culture. To explore the putative physiological role of pituitary CART, we compared levels of CART mRNA expression in lactating and nonlactating female rats. CART mRNA levels were significantly increased in the anterior pituitary and supraoptic nucleus of lactating rats. Furthermore, levels of CART in the systemic circulation were significantly elevated at the onset of lactation, peaked on d 10 of lactation and returned to baseline values 10 d after pups were weaned. The current study describes the cellular localization and regulation of CART expression and protein release from the rat pituitary gland. These findings suggest a putative role for CART in lactation.

scholarly journals Expression and regulation of glucocorticoid-induced leucine zipper in the developing anterior pituitary gland

2008 ◽  
Vol 42 (2) ◽  
pp. 171-183 ◽  
Author(s):  
Laura E Ellestad ◽  
Stefanie A Malkiewicz ◽  
H David Guthrie ◽  
Glenn R Welch ◽  
Tom E Porter
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Leucine Zipper ◽  
Pituitary Hormones ◽  
Neuroendocrine System ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Anterior Pituitary Hormone

The expression profile of glucocorticoid-induced leucine zipper (GILZ) in the anterior pituitary during the second half of embryonic development in the chick is consistent with in vivo regulation by circulating corticosteroids. However, nothing else has been reported about the presence of GILZ in the neuroendocrine system. We sought to characterize expression and regulation of GILZ in the chicken embryonic pituitary gland and determine the effect of GILZ overexpression on anterior pituitary hormone levels. Pituitary GILZ mRNA levels increased during embryogenesis to a maximum on the day of hatch, and decreased through the first week after hatch. GILZ expression was rapidly upregulated by corticosterone in embryonic pituitary cells. To determine whether GILZ regulates hormone gene expression in the developing anterior pituitary, we overexpressed GILZ in embryonic pituitary cells and measured mRNA for the major pituitary hormones. Exogenous GILZ increased prolactin mRNA above basal levels, but not as high as that in corticosterone-treated cells, indicating that GILZ may play a small role in lactotroph differentiation. The largest effect we observed was a twofold increase in FSH β subunit in cells transfected with GILZ but not treated with corticosterone, suggesting that GILZ may positively regulate gonadotroph development in a manner not involving glucocorticoids. In conclusion, this is the first report to characterize avian GILZ and examine its regulation in the developing neuroendocrine system. We have shown that GILZ is upregulated by glucocorticoids in the embryonic pituitary gland and may regulate expression of several pituitary hormones.

scholarly journals Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa
Keyword(s):  
Gene Expression ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Serum Concentrations ◽  
Gh Receptor ◽  
Its Gene ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

THYROID HORMONE REGULATES VASOACTIVE INTESTINAL PEPTIDE (VIP) mRNA LEVELS IN THE RAT ANTERIOR PITUITARY GLAND

Endocrinology ◽  
1989 ◽  
Vol 125 (4) ◽  
pp. 2221-2223 ◽  
Author(s):  
THOMAS P. SEGERSON ◽  
KAREN S.L. LAM ◽  
LUCINDA CACICEDO ◽  
NAOTO MINAMITANI ◽  
J. STEPHEN FINK ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Pituitary Gland ◽  
Vasoactive Intestinal Peptide ◽  
Anterior Pituitary ◽  
Anterior Pituitary Gland ◽  
Mrna Levels

Regulation of porcine insulin-like growth factor I and growth hormone receptor mRNA expression by energy status

1994 ◽  
Vol 266 (5) ◽  
pp. E776-E785 ◽  
Author(s):  
P. A. Weller ◽  
M. J. Dauncey ◽  
P. C. Bates ◽  
J. M. Brameld ◽  
P. J. Buttery ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Rates ◽  
Mrna Levels ◽  
Energy Status ◽  
Factor I ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Igf I ◽  
Class 1

Regulation of insulin-like growth factor I (IGF-I) and growth hormone (GH) receptor mRNA in liver and muscle by energy status was assessed in 2-mo-old pigs by altering thermoregulatory demand and energy intake over a 5-wk period to produce a range of plasma IGF-I concentrations from 3.5 +/- 0.7 to 28.9 +/- 6.2 nmol/l. These values were related directly to growth rates (0.06 +/- 0.02 to 0.44 +/- 0.01 kg/day) and total hepatic IGF-I mRNA levels. Increased growth rates were accompanied by an increase in hepatic class 1 and class 2 IGF-I mRNA levels and an increase in the ratio of class 2 to class 1 IGF-I mRNA in liver, suggesting a distinct role for class 2 expression in the endocrine growth response. High levels of class 1 transcripts and a virtual absence of class 2 transcripts characterized all muscle tissues examined, and there was no correlation with plasma IGF-I levels. This suggests that growth promotion in response to increased energy status is regulated via endocrine hepatic IGF-I rather than via a paracrine response. The levels of GH receptor mRNA were positively correlated with overall growth rate (P < 0.005) in liver and negatively correlated (P < 0.05) in muscle, indicating distinct tissue-specific effects of energy status.

Influence of Calcium Ions on Proopiomelanocortin mRNA Levels in Clonal Anterior Pituitary Cells

1988 ◽  
Vol 47 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Gerhard Von Dreden ◽  
Jean-Philippe Loeffler ◽  
Cornelia Grimm ◽  
Volker Höllt
Keyword(s):  
Calcium Ions ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Anterior Pituitary Cells
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