Elevated Plasma Levels of Pro-opiomelanocortin-Derived Peptides in Sheep following Hypothalamo-Pituitary Disconnection

Clarke, I. J.; Clements, Judith A.; Cummins, J. T.; Dench, Fiona; Smith, A. Ian; Robinson, Peter; Funder, John W.

doi:10.1159/000124693

Cited by 35 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both CRF and AVP have been shown to stimulate POMC peptide levels in the sheep [16], and although a negative regu latory factor has not yet been reported these data strongly sup port such a control mechanism. Our data are also supported by our previous observations [ 12] that in the OVX/HPD sheep ir-ACTH continues to be secreted from the AP in the absence of the stimulatory hypothalamic factors, and that plasma cortisol levels in OVX/HPD ewes are the same as [ 12] or slightly higher than 116] intact levels, suggesting that in the hypothalamopituitary intact sheep inhibitory hypothalamic factors exist which tonically suppress POMC mRNA levels.…”

Section: Discussionsupporting

confidence: 90%

“…Further evi dence for a nonhypothalamic, putatively direct effect of glu cocorticoids on the pituitary is provided in our previous study in which ovariectomized hypothalamopituitary disconnected (OVX-H PD) ewes treated with dexamethasone had lowered plasma ACTH levels compared to OVX controls [12], That study also suggested that the removal of hypothalamic input reReceived: June 20, 1988 Accepted after revision: January 18, 1989 suited in moderately elevated ACTH plasma levels. To investi gate further the direct effect of glucocorticoids, and to elucidate the contribution of hypothalamic factors to POMC gene ex pression, we have used our HPD sheep model [13] to study POMC mRNA levels in the sheep APand NIL.…”

mentioning

confidence: 96%

See 1 more Smart Citation

Glucocorticoid Regulation of Proopiomelanocortin Gene Expression in the Pituitary Gland of Hypothalamopituitary Intact and Hypothalamopituitary Disconnected Sheep

Mercer

Clements²,

Clarke³

et al. 1989

Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

Proopiomelanocortin (POMC) gene expression in the anterior pituitary (AP) gland has previously been shown to be positively regulated by CRF and AVP and negatively regulated by glucocorticoids. In the neurointermediate lobe () of the pituitary, however, POMC gene expression is under tonic inhibitory dopaminergic control. In the present study we have used hypothalamopituitary intact (HPI), ovariectomized (OVX), and OVX/hypothalamopituitary disconnected (OVX/HPD) ewes to examine direct (i.e. nonhypothalamic) effects of glucocorticoids on POMC gene expression in both the AP and the . There was no difference between POMC mRNA levels in intact and OVX sheep. In intact animals treated with dexamethasone, AP POMC mRNA levels were half those of controls. POMC mRNA levels were increased 3-fold in OVX/HPD sheep, compared with OVX, and lowered by dexamethasone to half OVX/HPD levels. In the , hypothalamopituitary disconnection resulted in slightly higher mean POMC mRNA levels than in intact animals but the large intragroup variation did not allow a significant change. Dexamethasone administration had no effect on levels of POMC mRNA in intact or OVX/HPD sheep.

show abstract

Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 96%

Glucocorticoid Regulation of Proopiomelanocortin Gene Expression in the Pituitary Gland of Hypothalamopituitary Intact and Hypothalamopituitary Disconnected Sheep

Mercer

Clements²,

Clarke³

et al. 1989

Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It may be assumed that the release of POMC peptides was increased in lesioned NILs, as was also reported in the hypothalamo-pituitary disconnected sheep [10]. A decrease in POMC peptide immunoreactivity in the IL was also observed after pituitary stalk transection [13] which also eliminates neural inputs to the IL.…”

supporting

confidence: 60%

Biosynthesis of pro-opiomelanocortin is increased in the rat intermediate pituitary following denervation

Seger

Kiss

Tol

et al. 1987

Neuroscience Letters

View full text Add to dashboard Cite

In order to study the effect of pituitary intermediate lobe denervation on pro-opiomelanocortin (POMC) biosynthesis and processing, radioactive amino acids were incorporated in vitro into whole neurointermediate lobe (NIL) explants obtained from hypothalamic lesioned rats and control animals. The lesion in the basal hypothalamus removed the neural input to the intermediate pituitary and cut the neurohypophyseal neurons. One week after the lesion, approximately a 3-fold increase in the rate of synthesis of POMC peptides was found in the NIL. The content of POMC peptides was decreased. The results imply that denervation increases the rate of POMC synthesis and release, without altering the pattern of proteolytic processing.The pro-opiomelanocortin (POMC)-synthesizing cells in the anterior lobe (AL) and intermediate lobe (IL) of the pituitary gland differ in the regulation of POMC gene expression, biosynthesis and release as well as in the nature of the peptides formed. In the rat AL, specific enzymatic cleavages of the precursor yield an aminoterminal glycopeptide of 74 amino acids (also referred to as 16K fragment), several forms of ACTH, and fl-LPH which is partially processed to fl-endorphin [9,11]. In the IL, POMC is processed more extensively: cleavage occurs at virtually all of the dibasic sites. The smaller products formed in this tissue are a non-glycosylated 49-residue N-terminal fragment [3], [Lysl]yaMSH [5], ct-MSH and CLIP (ACTH1s_39) [6], 7-LPH and several forms of endorphins [16]. Furthermore, POMC is subject to many post-translational modifications, namely glycosylation and phosphorylation [6], as well as amidation [12], acetylation [14] and endoproteolytic cleavages [16] following the formation of the major products.

show abstract

“…Since it is difficult to demonstrate inhibition of basal ACTH re lease by cortisol prior to 120 days, the findings of the present study do not clarify the role of cortisol in the di rect inhibition of ACTH release in the fetal sheep. It is of interest to note that dexamethasone administered to the adult HPD sheep inhibits ir-ACTH release [18]; this may indicate that the ACTH-producing cells have different sensitivities to exogenous glucocorticoids in the adult and fetal sheep. It must be noted that differences in circulat ing concentrations of cortisol in the fetal and adult sheep may be responsible for the suggested differences in gluco corticoid sensivitity.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cortisol Infusion on the Pituitary-Adrenal Axis of the Hypothalamo-Pituitary-Disconnected Fetal Sheep

et al. 1992

Self Cite

View full text Add to dashboard Cite

In order to determine whether cortisol acts directly at the level of the fetal pituitary to promote pars distalis corticotroph maturation, we have infused cortisol into the hypothalamo-pituitary-disconnected (HPD) fetal sheep from 111 to 117 days of gestation. In this study we have measured fetal plasma cortisol and immunoreactive adrenocorticotrophic hormone (ir-ACTH) concentrations between 105 and 116 days of gestation, and we have determined the proportions of adult- and fetal-type corticotrophs in the pars distalis of catheter control fetuses and in HPD fetuses infused with either saline (HPD + SAL) or cortisol (2 mg/day; HPD + F). The fetal plasma cortisol concentrations did not change significantly following HPD. The mean fetal plasma cortisol concentration between 113 and 116 days was threefold higher in the HPD + F fetuses than that measured in HPD fetuses. Following HPD, fetal plasma ir-ACTH concentrations were significantly higher than in catheter control fetuses. Despite the significant elevation in plasma cortisol concentrations in HPD + F fetuses between 113 and 116 days, plasma ir-ACTH concentrations were not different in these fetuses from HPD fetuses infused with saline. At 117 days of gestation in HPD + F fetuses, the proportion of fetal-type corticotrophs in the pars distalis was significantly less than in the HPD + SAL fetuses; however, there was no significant change in the proportion of adult-type corticotrophs in the pars distalis following cortisol infusion. We have shown that cortisol has a direct trophic effect on the maturation of the pars distalis corticotrophs; however, the full maturation of these cells requires an intact hypothalamo-pituitary axis. These findings demonstrate the importance of the fetal hypothalamus in anterior pituitary corticotroph maturation during the last third of gestation.

show abstract

Elevated Plasma Levels of Pro-opiomelanocortin-Derived Peptides in Sheep following Hypothalamo-Pituitary Disconnection

Cited by 35 publications

References 24 publications

Glucocorticoid Regulation of Proopiomelanocortin Gene Expression in the Pituitary Gland of Hypothalamopituitary Intact and Hypothalamopituitary Disconnected Sheep

Glucocorticoid Regulation of Proopiomelanocortin Gene Expression in the Pituitary Gland of Hypothalamopituitary Intact and Hypothalamopituitary Disconnected Sheep

Biosynthesis of pro-opiomelanocortin is increased in the rat intermediate pituitary following denervation

Effect of Cortisol Infusion on the Pituitary-Adrenal Axis of the Hypothalamo-Pituitary-Disconnected Fetal Sheep

Contact Info

Product

Resources

About