Transcriptional and post-transcriptional mechanisms regulating the rat pituitary vasopressin V1b receptor gene

Aguilera, Greti; Volpi, Simona; Rabadan‐Diehl, Cristina

doi:10.1677/jme.0.0300099

Cited by 24 publications

(17 citation statements)

References 24 publications

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“…The plausibility of such an explanation is given increased credence from the finding of a number of open reading frames within the MC1R 5′‐UTR of the endogenous human MC1R transcript (Smith et al., 2001). The presence of such upstream AUG triplets in the mRNA of murine MC1R (Rouzaud et al., 2003) and other G‐protein‐coupled receptors has been shown to inhibit translation (Aguilera et al., 2003; Xu et al., 2001).…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of MC1R gene expression in human skin cell cultures

Roberts

Newton

Beaumont

et al. 2005

Pigment Cell Research

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To address the issue of melanocortin-1 receptor (MC1R) expression in non-melanocytic cells, we have quantitatively evaluated the relative expression levels of both MC1R mRNA and protein in a subset of different cell types. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at high cycle numbers, we detected MC1R mRNA in all cell types examined, including human embryonic kidney-293 (HEK 293) cells, a cell type widely used as a negative control in melanocortin expression studies. Quantitative real-time PCR revealed the highest levels of MC1R transcripts were in melanocytic cells, whereas the keratinocyte and fibroblast cell cultures examined had only a low level of expression, similar to that of HEK 293 cells. Antibody mediated detection of MC1R protein in membrane extracts demonstrated exogenous receptor in MC1R transfected cell lines, as well as endogenous MC1R in melanoma cells. However, radioligand binding procedures were required to detect MC1R protein of normal human melanocytes and no surface expression of MC1R was detected in any of the non-melanocytic cells examined. This was consistent with their low level of mRNA, and suggests that, if present, the levels of surface receptor are significantly lower than that in melanocytes. The capacity of such limited levels of MC1R protein to influence non-melanocytic skin cell biology would likely be severely compromised. Indeed, the MC1R agonist [NIe(4), D-Phe(7)] alpha-melanocyte stimulating hormone (NDP-MSH) was unable to elevate intracellular cyclic adenosine monophosphate (cAMP) levels in the keratinocyte and fibroblast cells examined, whereas a robust increase was elicited in melanocytes. Although there are a variety of cell types with detectable MC1R mRNA, the expression of physiologically significant levels of the receptor may be more restricted than the current literature indicates, and within epidermal tissue may be limited to the melanocyte.

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Section: Discussionmentioning

confidence: 99%

Quantitative analysis of MC1R gene expression in human skin cell cultures

Roberts

Newton

Beaumont

et al. 2005

Pigment Cell Research

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“…We also observed no significant differences of V1b mRNA levels between FR50 rats and control animals. However, the above hypothesis cannot be excluded since it has recently been shown that a discrepancy occurs between pituitary V1b mRNA levels and VP binding sites during adaptation of the HPA axis to stress in rats [59]. This result could suggest that V1b activity is predominantly regulated via post-transcriptional mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Food Deprivation Induces Marked Alterations of the Hypothalamo-Pituitary-Adrenal Axis in 8-Month-Old Male Rats both under Basal Conditions and after a Dehydration Period

et al. 2004

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Dehydration is a classic homeostatic stressor in rats that leads to a series of endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. During the last decade, it has been well established that perinatal food restriction is associated with the onset of diseases in adults. Our previous demonstration of long-term alterations in HPA axis activity in both basal conditions and after a 72-hour dehydration period in 4-month-old rats exposed to a 50% maternal food restriction (FR50) in late gestation and lactation prompted us to investigate whether such perinatal undernutrition further affects HPA axis activity in mature animals. As previously described in 4-month-old rats under basal conditions, 8-month-old FR50 rats showed reduced body weight and an enhanced ratio between mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA levels in the hippocampus, as well as increased pro-opiomelanocortin (POMC) mRNA levels in the adenohypophysis. In addition, numerous additional alterations appeared in mature rats. In the hypothalamus, levels of vasopressin (VP) mRNAs were increased both in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). In the adenohypophysis, GR and prohormone-convertase 2 (PC2) mRNA levels were significantly increased, whereas prohormone-convertase 1 (PC1) mRNA was not affected by maternal undernutrition. Interestingly, undernourished animals exhibited high plasma levels of total and free corticosterone in spite of normal corticotropin (ACTH) levels, an indication that HPA basal activity is enhanced by maternal undernutrition in 8-month-old animals. Dehydration for 72 h induced a rise in ACTH plasma levels, but did not modify total and free corticosterone plasma levels in 8-month-old FR50 animals. In the adenopituitary, POMC mRNA levels were decreased after dehydration but PC1 mRNA levels were unaffected. The present study indicates that maternal food restriction during the perinatal period dramatically affects the activity of the HPA axis until the age of 8 months. We speculate that higher basal HPA activity and an inadequate HPA response after dehydration in mature animals may contribute to diseases such as hypertension, known to develop with aging in perinatally growth-restricted rats.

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“…This is similar to observations with other G-protein coupled receptors, such as the V1b vasopressin receptor and the CRH receptors in which mRNA levels decrease following acute stress (Rabadan-Diehl et al, 1995; Rabadan-Diehl et al, 1996). This suggests that as with the latter receptors, regulation is predominantly at the translational level rather than transcriptional (Aguilera et al, 2003). The decrease in MC2R mRNA could be due to mRNA utilization during translation to newly synthesized protein.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of episodic glucocorticoid secretion

Liu

Smith

Huang

et al. 2013

Molecular and Cellular Endocrinology

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Circadian and ultradian variations of basal glucocorticoid secretion and transient elevations during stress are essential for homeostasis. Using intronic qRT-PCR to measure changes in primary transcript (hnRNA) we have shown that secretory events induced by stress or ACTH injection are followed by episodic increases in transcription of rate limiting steroidogenic proteins, such as steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage and melanocortin receptor associated protein. These transcriptional episodes imply rapid turnover of steroidogenic proteins and the need of de novo synthesis following each secretory event. In addition to episodic ACTH secretion, it is likely that intracellular feedback mechanisms at the adrenal fasciculata level contribute to the generation of episodes of transcription. The time relationship between activation and translocation of the CREB co-activator, transducer of regulated CREB activity (TORC) to the nucleus preceding transcriptional episodes suggest the involvement of TORC in the transcriptional activation of StAR and other steroidogenic proteins.

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Transcriptional and post-transcriptional mechanisms regulating the rat pituitary vasopressin V1b receptor gene

Cited by 24 publications

References 24 publications

Quantitative analysis of MC1R gene expression in human skin cell cultures

Quantitative analysis of MC1R gene expression in human skin cell cultures

Perinatal Food Deprivation Induces Marked Alterations of the Hypothalamo-Pituitary-Adrenal Axis in 8-Month-Old Male Rats both under Basal Conditions and after a Dehydration Period

Transcriptional regulation of episodic glucocorticoid secretion

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