scholarly journals Somatotroph recruitment by glucocorticoids involves induction of growth hormone gene expression and secretagogue responsiveness

2001 ◽  
Vol 169 (3) ◽  
pp. 499-509 ◽  
Author(s):  
TE Porter ◽  
CE Dean ◽  
MM Piper ◽  
KL Medvedev ◽  
S Ghavam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Anterior Pituitary ◽  
Precursor Cells ◽  
Pituitary Cells ◽  
Caudal Lobe ◽  
Releasing Hormone ◽  
Gh Secretagogues ◽  
Gh Cells ◽  
Gh Gene

Prior research indicates that growth hormone (GH) cell differentiation can be induced prematurely by treatment with glucocorticoids in vitro and in vivo. However, the nature of these responses has not been fully characterized. In this study, the time course of corticosterone induction of GH-secreting cells in cultures of chicken embryonic pituitary cells, responsiveness of differentiated somatotrophs to GH secretagogues, localization of somatotroph precursor cells within the pituitary gland, and the effect of corticosterone on GH gene expression were determined to better define the involvement of glucocorticoids in somatotroph recruitment during development. Anterior pituitary cells from embryonic day 12 chicken embryos were cultured in 10(-9) M corticosterone for 4 to 48 h and were then subjected to reverse haemolytic plaque assays (RHPAs) for GH. Corticosterone treatment for as short as 16 h increased the percentage of GH cells compared with the control. When corticosterone was removed after 48 h and cells were cultured for an additional 3 days in medium alone, the percentage of GH secretors decreased but remained greater than the proportion of somatotrophs among cells that were never treated with corticosterone. To determine if prematurely differentiated somatotrophs were responsive to GH secretagogues, cells were exposed to corticosterone for 48 h and then subjected to GH RHPAs in the presence or absence of GH-releasing hormone (GHRH) or thyrotropin-releasing hormone (TRH). Approximately half of the somatotrophs induced to differentiate with corticosterone subsequently released more GH in response to GHRH and TRH than in their absence. The somatotroph precursor cells were localized within the anterior pituitary by culturing cells from the caudal lobe and cephalic lobe of the anterior pituitary separately. Corticosterone induction of GH cells was substantially greater in cultures derived from the caudal lobe of the anterior pituitary, where somatotroph differentiation normally occurs. GH gene expression was evaluated by ribonuclease protection assay and by in situ hybridization. Corticosterone increased GH mRNA in cultured cells by greater than fourfold. Moreover, corticosterone-induced somatotroph differentiation involved GH gene expression in cells not expressing GH mRNA previously, and the extent of somatotroph differentiation was augmented by treatment with GHRH in combination with corticosterone. We conclude that corticosterone increases the number of GH-secreting cells within 16 h, increases GH gene expression in cells formerly not expressing this gene, confers somatotroph sensitivity to GHRH and TRH, and induces GH production in a precursor population found primarily in the caudal lobe of the anterior pituitary, a site consistent with GH localization in adults. These findings support the hypothesis that glucocorticoids function to induce the final stages in the differentiation of fully functional somatotrophs from cells previously committed to this lineage.

PKC and ERK are differentially involved in gonadotropin-releasing hormone-induced growth hormone gene expression in the goldfish pituitary

2005 ◽  
Vol 289 (6) ◽  
pp. R1625-R1633 ◽  
Author(s):  
Christian Klausen ◽  
Takeshi Tsuchiya ◽  
John P. Chang ◽  
Hamid R. Habibi
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Primary Cultures ◽  
Gonadotropin Releasing Hormone ◽  
Growth Hormone Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Gh Gene

Gonadotropin-releasing hormone (GnRH) is produced by the hypothalamus and stimulates the synthesis and secretion of gonadotropin hormones. In addition, GnRH also stimulates the production and secretion of growth hormone (GH) in some fish species and in humans with certain clinical disorders. In the goldfish pituitary, GH secretion and gene expression are regulated by two endogenous forms of GnRH known as salmon GnRH and chicken GnRH-II. It is well established that PKC mediates GnRH-stimulated GH secretion in the goldfish pituitary. In contrast, the signal transduction of GnRH-induced GH gene expression has not been elucidated in any model system. In this study, we demonstrate, for the first time, the presence of novel and atypical PKC isoforms in the pituitary of a fish. Moreover, our results indicate that conventional PKCα is present selectively in GH-producing cells. Treatment of primary cultures of dispersed goldfish pituitary cells with PKC activators (phorbol ester or diacylglycerol analog) did not affect basal or GnRH-induced GH mRNA levels, and two different inhibitors of PKC (calphostin C and GF109203X) did not reduce the effects of GnRH on GH gene expression. Together, these results suggest that, in contrast to secretion, conventional and novel PKCs are not involved in GnRH-stimulated increases in GH mRNA levels in the goldfish pituitary. Instead, PD98059 inhibited GnRH-induced GH gene expression, suggesting that the ERK signaling pathway is involved. The results presented here provide novel insights into the functional specificity of GnRH-induced signaling and the regulation of GH gene expression.

scholarly journals Evidence that lactotrophs do not differentiate directly from somatotrophs during chick embryonic development

2004 ◽  
Vol 183 (2) ◽  
pp. 417-425 ◽  
Author(s):  
Xiaoqin Fu ◽  
Shotaro Nishimura ◽  
Tom E Porter
Keyword(s):  
Growth Hormone ◽  
Embryonic Development ◽  
Anterior Pituitary ◽  
Intermediate Cell ◽  
Pituitary Cells ◽  
Cell Type ◽  
Caudal Lobe ◽  
Pituitary Development ◽  
Gh Cells ◽  
Cephalic Lobe

It is generally accepted that, in mammals, lactotrophs differentiate from somatotrophs through an intermediate cell type, the mammosomatotroph. However, little information exists about mammosomatotrophs and their relationship with lactotroph development in non-mammalian vertebrates. We reported previously that corticosterone (CORT) can induce both somatotroph and lactotroph differentiation in cultures of chicken embryonic pituitary cells. Our current objectives were to determine the abundance of mammosomatotrophs during chicken pituitary development, to identify mammosomatotrophs during CORT induction of lactotrophs, and to explore whether lactotrophs induced by CORT are derived from somatotrophs. Cells that produced prolactin (PRL) only, growth hormone (GH) only or both hormones simultaneously were detected by three approaches – dual immunofluorescence, a combination of immunofluorescence and immunocytochemistry (ICC), and by ICC using combinations of antibodies to GH and PRL. Mammosomatotrophs were not detected between embryonic day (E) 16 and E20, even though lactotrophs increased from nearly absent to greater than 10% of all pituitary cells during this period. CORT induced more than 10% of all E13 pituitary cells to produce PRL, while the percentage of mammosomatotrophs remained at less than 1% of all cells. When cells from the cephalic and caudal lobes of the anterior pituitary were treated separately, CORT increased GH cells in cultures from the caudal lobe. No PRL cells were found in the caudal lobe. In the cephalic lobe, CORT increased lactotrophs, while GH cells were barely detected. In summary, mammosomatotrophs are rare during chicken pituitary development, and CORT does not induce lactotrophs from somatotrophs. These findings indicate that, unlike in mammals, lactotrophs do not differentiate from somatotrophs during chicken embryonic development.

Thyrotropin-Releasing Hormone Gene Expression in Cultured Anterior Pituitary Cells: Role of Gender

1995 ◽  
Vol 61 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Thomas O. Bruhn ◽  
Jan M.M. Rondeel ◽  
Thomas G. Bolduc ◽  
Ivor M.D. Jackson
Keyword(s):  
Gene Expression ◽  
Anterior Pituitary ◽  
Thyrotropin Releasing Hormone ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells

172 IN VITRO EXPOSURE TO XENOESTROGENS INDUCES GROWTH HORMONE TRANSCRIPTION AND RELEASE VIA AN ESTROGEN RECEPTOR-DEPENDENT PATHWAY IN RAT PITUITARY GH3 CELLS

2008 ◽  
Vol 20 (1) ◽  
pp. 166
Author(s):  
V.-H. Dang ◽  
E.-B. Jeung
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Estrogen Receptor ◽  
Gene Transcription ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Rat Pituitary ◽  
In Vitro Exposure ◽  
Gh Gene

The term endocrine disruptor (ED) has been used widely to characterize natural and synthetic environmental compounds that may interfere with the endocrine system(s) of humans and wildlife. In previous studies, we demonstrated that in vitro single exposure to EDs induces CaBP-9k expression, a useful biomarker for detecting the estrogenic activities of EDs in rat pituitary GH3 cells. Here we employ the identical model to examine the effects of EDs in the regulation of growth hormone (GH) gene expression, an important hormone in growth, development, and body composition. We measured levels of GH mRNA transcription and GH release using semi-quantitative RT-PCR and EIA kit, respectively. GH3 cells were treated with alkyphenols (APs), i.e., octyl-phenol (OP), nonyl-phenol (NP), and bisphenol A (BPA), in a dose-dependent manner (10–5, 10–6, and 10–7 M) and harvested following 24 h of treatment. Cells were also exposed to a high concentration (10–5 M) of OP, NP, or BPA and harvested at various time points (1, 3, 6, 12, and 24 h). An anti-estrogen, ICI 182780 (10–7 M) was used to examine the potential involvement of estrogen receptor (ER) in the induction of GH by EDs through an ER-mediated pathway. The data were analyzed by one-way ANOVA, followed by Tukey's multiple comparison. OP, NP, and BPA induced a significant increase in GH gene expression at high (10–5 M) and medium (10–6 M) doses at 24 h. ED-exposure induced a marked increase in GH gene transcription as early as 6 h and peaked at 12 h. Co-treatment with ICI 182780 significantly attenuated ED-induced GH expression in GH3 cells. Interestingly, the level of in vitro GH release was increased significantly at 24 h in response to OP, NP, or BPA, whereas co-treatment with ICI 182780 significantly diminished ED-induced GH secretion in GH3 cells, indicating that ER may play a part in both GH gene transcription and GH release in these cells. Here we demonstrate for the first time that single in vitro exposure to OP, NP, or BPA results in an increase in GH expression at 24 h in GH3 rat pituitary cells. These results may provide new insight into the mode of ED action in GH gene regulation as well as the biological pathway underlying these molecular events. Furthermore, data showing GH responsiveness evoked by EDs supports the aim to develop an assay for use in predicting adverse health effects of EDs in humans and wildlife.

scholarly journals Cytochemical Studies of the Effects of Activin on Gonadotropin-releasing Hormone (GnRH) Binding by Pituitary Gonadotropes and Growth Hormone Cells

1997 ◽  
Vol 45 (12) ◽  
pp. 1603-1610 ◽  
Author(s):  
Gwen V. Childs ◽  
Geda Unabia
Keyword(s):  
Growth Hormone ◽  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Target Cells ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Average Area ◽  
Gnrh Receptors ◽  
Gh Cells

Activin stimulates the synthesis and secretion of follicle-stimulating hormone (FSH). It inhibits the synthesis and release of growth hormone (GH). It acts on gonadotropes by stimulating the synthesis of gonadotropin-releasing hormone (GnRH) receptors. To test activin's effects on GnRH target cells, pituitary cells from diestrous or proestrous rats were exposed to media with and without 60 ng/ml activin for 24 hr and stimulated with biotinylated GnRH (Bio-GnRH). The populations were double-labeled for Bio-GnRH and/or luteinizing hormone-β (LH-β), FSH-β, or GH antigens. In both diestrous and proestrous rats, activin stimulated more LH and FSH cells and increased the percentages of GnRH target cells. In diestrous rats, activin stimulated increases in the average area and density of Bio-GnRH label on target cells. In addition, more FSH, LH, and GH cells bound Bio-GnRH. The increment in binding by gonadotropes was not as great as that normally seen from diestrus to proestrus, suggesting that additional factors (such as estradiol) may be needed. These data suggest that activin plays an important role in the augmentation of Bio-GnRH target cells normally seen before ovulation. Its actions on GH cells may reflect a role in the transitory change from a somatotrope to a somatogonadotrope that is seen from diestrus to proestrus.

Signaling mechanisms for α2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells

2007 ◽  
Vol 292 (6) ◽  
pp. E1750-E1762 ◽  
Author(s):  
Xinyan Wang ◽  
Mable M. S. Chu ◽  
Anderson O. L. Wong
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Adenylate Cyclase ◽  
Grass Carp ◽  
Promoter Activity ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Gh Gene

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent growth hormone (GH)-releasing factor in lower vertebrates. However, its functional interactions with other GH regulators have not been fully characterized. In fish models, norepinephrine (NE) inhibits GH release at the pituitary cell level, but its effects on GH synthesis have yet to be determined. We examined adrenergic inhibition of PACAP-induced GH secretion and GH gene expression using grass carp pituitary cells as a cell model. Through activation of pituitary α2-adrenoreceptors, NE or the α2-agonist clonidine reduced both basal and PACAP-induced GH release and GH mRNA expression. In carp pituitary cells, clonidine also suppressed cAMP production and intracellular Ca2+ levels and blocked PACAP induction of these two second messenger signals. In GH3 cells transfected with a reporter carrying the grass carp GH promoter, PACAP stimulation increased GH promoter activity, and this stimulatory effect could be abolished by NE treatment. In parallel experiments, clonidine reduced GH primary transcript and GH promoter activity without affecting GH mRNA stability, and these inhibitory actions were mimicked by inhibiting adenylate cyclase (AC), blocking protein kinase A (PKA), removing extracellular Ca2+ in the culture medium, or inactivating L-type voltage-sensitive Ca2+ channels (VSCC). Since our recent studies have shown that PACAP can induce GH secretion in carp pituitary cells through cAMP/PKA- and Ca2+/calmodulin-dependent mechanisms, these results, taken together, suggest that α2-adrenergic stimulation in the carp pituitary may inhibit PACAP-induced GH release and GH gene transcription by blocking the AC/cAMP/PKA pathway and Ca2+ entry through L-type VSCC.

Time- and dose-related effects of gonadotropin-releasing hormone on growth hormone and gonadotropin subunit gene expression in the goldfish pituitary

2002 ◽  
Vol 80 (9) ◽  
pp. 915-924 ◽  
Author(s):  
Christian Klausen ◽  
John P Chang ◽  
Hamid R Habibi
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Molecular Forms ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Induced Responses ◽  
Releasing Hormone ◽  
Significant Difference

The goldfish brain contains two molecular forms of gonadotropin-releasing hormone (GnRH): salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II). In a preliminary report, we demonstrated the stimulation of gonadotropin hormone (GtH) subunit and growth hormone (GH) mRNA levels by a single dose of GnRH at a single time point in the goldfish pituitary. Here we extend the work and demonstrate time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH gene expression in vivo and in vitro. The present study demonstrates important differences between the time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels. Using primary cultures of dispersed pituitary cells, the minimal effective dose of cGnRH-II required to stimulate GtH subunit mRNA levels was found to be 10-fold lower than that of sGnRH. In addition, the magnitudes of the increases in GtH subunit and GH mRNA levels stimulated by cGnRH-II were found to be higher than the sGnRH-induced responses. However, no significant difference was observed between sGnRH and cGnRH-II-induced responses in vivo. Time-related studies also revealed significant differences between sGnRH- and cGnRH-II-induced production of GtH subunit and GH mRNA in the goldfish pituitary. In general, the present study provides novel information on time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels and provides a framework for further investigation of GnRH mechanisms of action in the goldfish pituitary.Key words: gonadotropin-releasing hormone, gonadotropin hormone, growth hormone, gene expression, goldfish.

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