Ontogeny of pro-opiomelanocortin (POMC) gene expression and translated products adrenocorticotrophin (ACTH) and α-melanocyte stimulating hormone (α-MSH) in the ovine fetal pituitary gland

1998 ◽  
Vol 10 (3) ◽  
pp. 233 ◽  
Author(s):  
D. M. Hagan ◽  
A. N. Brooks

This study sought to determine the ontogeny of pro-opiomelanocortin (POMC) mRNA by in situ hybridization, and the expression of α–melanocyte stimulating hormone (α-MSH) and adrenocorticotrophin (ACTH) by immunohistochemistry, in the ovine fetal pituitary gland. Detection of POMC mRNA, and of ACTH and α-MSH immunoreactivity was first noted at Day 40 of gestation in the pars intermedia (PI) and the pars distalis (PD). After Day 70, α-MSH immunoreactivity was confined to the PI whereas POMC mRNA and ACTH immunostaining remained in both the PI and the PD. Increases (P < 0.05) of POMC mRNA expression were observed in the PI between Days 50–70 and levels then remained constant to Day 141 (term, 145 days). In the basal region of the PD, POMC mRNA expression was high at Day 40, declined (P < 0.01) by Day 50 and then increased progressively to Day 141 of gestation. The proportion of ACTH-immunopositive cells in the PD also fell from 14% at Day 40 to 11.4% at Day 70 and then increased to 15.3% by Day 141. In contrast, neither the level of POMC mRNA expression nor the percentage of corticotrophs changed in the region of the PD immediately adjacent to the PI. These data provide evidence for differential processing of POMC in a tissue-specific manner during early fetal pituitary development.

1995 ◽  
Vol 147 (1) ◽  
pp. 139-146 ◽  
Author(s):  
S G Matthews ◽  
J R G Challis

Abstract It is well established that corticotrophin-releasing hormone and vasopressin can induce both synthesis and release of ACTH from the ovine pituitary gland, and that glucocorticoids can inhibit these responses. Changes in the abundance, localization and distribution of proopiomelanocortin (POMC) mRNA and prolactin (PRL) mRNA in the ovine fetal pituitary were examined by in situ hybridization following hypoxaemia applied in the presence or absence of concomitant cortisol in late gestation (day 135). Fetuses were distributed amongst four groups; saline-infused/normoxaemic, cortisol-infused/normoxaemic (0·3 mg/h), saline-infused/hypoxaemic and cortisol-infused/hypoxaemic. Hypoxaemia (6 h) was induced by reducing the maternal PaO2, resulting in a 6–8 mmHg decrease in fetal arterial PO2. Fetal infusions were commenced 5 h prior to and maintained throughout the treatment period. Hypoxaemia, which elevated fetal plasma ACTH and cortisol, caused a significant (P<0·05) increase in POMC mRNA in the pars distalis (PD), but was without effect on POMC mRNA in the pars intermedia (PI). Cortisol infusion attenuated the hypoxaemiainduced increase in POMC mRNA in the PD, but was without effect on non-stimulated steady-state POMC mRNA levels in either the PD or PI. PRL mRNA was only present in the PD and significantly (P<0·05) increased after cortisol infusion and hypoxaemia. In conclusion (i) POMC and PRL mRNA in the PD are increased following moderate hypoxaemia, (ii) cortisol attenuates changes in POMC mRNA but not PRL mRNA in the PD following hypoxaemia and (iii) cortisol increases PRL mRNA levels in the PD. Synthesis of POMC and PRL in the fetal PD is highly sensitive to homeostatic perturbations and glucocorticoids in late gestation. Journal of Endocrinology (1995) 147, 139–146


1986 ◽  
Vol 43 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Hans J. Leenders ◽  
Jan J.W. Janssens ◽  
Henry J.M. Theunissen ◽  
Bruce G. Jenks ◽  
Abraham P. van Overbeeke

2002 ◽  
Vol 283 (1) ◽  
pp. E165-E171 ◽  
Author(s):  
Alison C. Holloway ◽  
David C. Howe ◽  
Gabriel Chan ◽  
Vicki L. Clifton ◽  
Roger Smith ◽  
...  

We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.


1970 ◽  
Vol 46 (2) ◽  
pp. 201-NP ◽  
Author(s):  
A. HOWE ◽  
A. J. THODY

SUMMARY The changes in the content of melanocyte-stimulating hormone (MSH) and histology of the neuro-intermediate (n.i.) lobe were followed in rats which drank 2% sodium chloride for periods from 1–15 days. The pars intermedia showed a biphasic response. During the initial phase of 1–4 days there was a rapid rise in the MSH content, by 153% in the first day, falling back to control level by 4 days. These fluctuations were paralleled by an increase in the normally small numbers of Type 2 cells and at the same time numerous Type I cells showed hypertrophy and degranulation. After 4 days on saline there was a second rise in the MSH content, which was still evident at 15 days; during this second period the number of Type 2 cells declined to normal levels. The degranulated Type 1 cells also disappeared, most of Type 1 being smaller in size and intensely PAS-positive. After the ingestion of saline it apparently takes several days before the pars intermedia adapts to a new level of activity. The likely significance of these changes and the possibility of a relationship between the pars intermedia and the neurohypophysis are discussed.


1995 ◽  
Vol 14 (3) ◽  
pp. 323-336 ◽  
Author(s):  
F Lü ◽  
K Yang ◽  
V K M Han ◽  
J R G Challis

ABSTRACT Activation of the fetal pituitary-adrenal axis is crucial for fetal organ maturation and the onset of parturition in sheep. Many factors including corticotrophin-releasing hormone (CRH) and arginine vasopressin secreted from the hypothalamus, and growth factors produced within the pituitary may be involved in the regulation of maturation of the fetal pituitary gland. IGFs have mitogenic and differentiation-promoting capacities in a variety of organs and are synthesized as paracrine factors within developing tissues. However, there is little information concerning the synthesis, distribution, regulation and function of IGFs in the fetal pituitary gland at different times during pregnancy. Therefore, we have localized IGF-I and IGF-II mRNAs and peptides, and determined the effect of cortisol on the level of IGF-II mRNAs in the pituitary glands of developing sheep fetuses. We examined the possible effects of IGFs on corticotroph function in cultures of adenohypophysial cells from term fetuses. Seven species of IGF-II transcripts of 1·2–6·0 kb were identified by Northern blot analysis in the pituitary gland of fetuses between day 60 of gestation and term (day 145). The levels of IGF-II mRNAs did not change significantly during pregnancy, although there was a trend for the presence of higher levels of IGF-II mRNAs at day 60 of gestation. IGF-I mRNA was not detectable. By in situ hybridization, IGF-II mRNA was localized to non-endocrine cells and to cells lining the blood vessels of the pars distalis, to some presumed endocrine cells in the pars distalis and pars intermedia, and to clusters of cells in the pars nervosa. In contrast, IGF-I and IGF-II peptides were detected in the presumed endocrine cells in the pars distalis and pars intermedia but not in the pars nervosa. Incubation of adenohypophysial cells from term fetuses with IGF-I, but not IGF-II, for 48 h increased specific 125I-Tyr-ovine CRH binding. However, neither IGF-I nor IGF-II had any significant effects on the basal or CRH-stimulated immunoreactive (ir)-ACTH output, the level of POMC mRNA or the number of ir-ACTH positive cells. Infusion of cortisol to fetuses starting at day 96 of gestation for 100 h or at days 120–125 of gestation for 84 h did not affect the level of IGF-II mRNAs in the pars distalis but decreased the levels of POMC mRNA. These results are consistent with IGFs having the potential to influence fetal pituitary function, although probably on cell types other than the corticotrophs. The likely sources of IGFs may be predominantly local (IGF-II) or from extrapituitary sources (IGF-I).


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