Proopiomelanocortin, prolactin and growth hormone messenger ribonucleic acid levels in the fetal sheep pituitary during late gestation

1993 ◽  
Vol 129 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Jennifer J Merei ◽  
Alix Rao ◽  
lain J Clarke ◽  
I Caroline McMillen
Keyword(s):  
Growth Hormone ◽  
Ribonucleic Acid ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Messenger Ribonucleic Acid ◽  
Pomc Mrna ◽  
Significant Difference ◽  
The Mean ◽  
Pomc Gene

We have measured the relative levels of proopiomelanocortin (POMC), prolactin (PRL) and growth hormone (GH) messenger ribonucleic acid (mRNA) in the anterior and neurointermediate lobes of the fetal pituitary during the last 2–3 weeks of gestation. The mean POMC mRNA/18S RNA ratio in the fetal anterior pituitary was significantly greater (p<0.02) at 130–136 days (0.90±0.08; N=9) than at 141–143 days of gestation (0.67±0.07; N=6). In contrast, the mean PRL mRNA/18S RNA ratio increased significantly (p< 0.02) ) between 130 and 136 days (0.31±0.05; N = 9) when compared with 141–143 days of gestation (0.58±0.10; N = 6). There was no significant difference, however, between the mean GH mRNA/18S RNA ratio in fetal anterior pituitaries at 130–136 days (0.95±0.04; N = 9) when compared with 141–143 days of gestation (1.08±0.14; N=6). The POMC mRNA/18S RNA ratio in the neurointermediate lobes was seven-, five- and tenfold higher than in anterior pituitaries at 130–134, 135–136 and 141–143 days of gestation, respectively. We hypothesize that elevated circulating cortisol levels after 140 days of gestation act in the slow time domain (i.e. over days) to suppress POMC gene expression and that the increase in fetal pituitary PRL mRNA levels may be a consequence of oestrogen stimulation in late gestation.

Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol administration to late-gestation ovine fetus

1998 ◽  
Vol 274 (3) ◽  
pp. E417-E425 ◽  
Author(s):  
T. M. Jeffray ◽  
S. G. Matthews ◽  
G. L. Hammond ◽  
J. R. G. Challis
Keyword(s):  
Plasma Cortisol ◽  
Late Gestation ◽  
Pars Intermedia ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Negative Feedback Regulation ◽  
Fetal Sheep ◽  
Pomc Mrna ◽  
Free Cortisol ◽  
Ovine Fetus

Plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH) rise in the late-gestation sheep fetus at approximately the same time as there is an increase in the plasma levels of corticosteroid- binding globulin (CBG). We hypothesized that intrafetal cortisol infusion during late pregnancy would stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and diminish glucocorticoid negative-feedback regulation of the fetal pituitary, leading to an increase in plasma ACTH concentrations. Cortisol was infused into chronically catheterized fetal sheep beginning at 126.1 ± 0.5 days of gestation and continued for 96 h. Control fetuses were infused with saline. In cortisol-infused fetuses, the plasma cortisol concentrations rose significantly from control levels (4.4 ± 0.6 ng/ml) to 19.3 ± 3.1 ng/ml within 24 h and remained significantly elevated throughout the infusion period. Plasma immunoreactive (ir) ACTH concentrations were significantly elevated in cortisol-infused fetuses within 24–48 h and remained significantly higher than in controls throughout the 96-h experimental period. Plasma free cortisol concentrations increased 10-fold and remained significantly elevated in cortisol-infused animals, despite a rise in plasma corticosteroid-binding capacity. Levels of pituitary proopiomelanocortin (POMC) mRNA in the fetal pars distalis and pars intermedia were 96 and 38% lower, respectively, after 96 h of cortisol infusion. Therefore physiological elevations of plasma cortisol, in the late-gestation ovine fetus, lead to increases in mean plasma irACTH concentrations, but this is not associated with increases in fetal pituitary POMC mRNA levels.

Levels of pro-opiomelanocortin and prolactin mRNA in the fetal sheep pituitary following hypoxaemia and glucocorticoid treatment in late gestation

1995 ◽  
Vol 147 (1) ◽  
pp. 139-146 ◽  
Author(s):  
S G Matthews ◽  
J R G Challis
Keyword(s):  
Late Gestation ◽  
Pars Intermedia ◽  
Mrna Levels ◽  
Glucocorticoid Treatment ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pomc Mrna ◽  
Highly Sensitive ◽  
Ovine Fetal

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

Pro-opiomelanocortin messenger RNA levels increase in the fetal sheep pituitary during late gestation

1991 ◽  
Vol 131 (3) ◽  
pp. 483-489 ◽  
Author(s):  
K. Yang ◽  
J. R. G. Challis ◽  
V. K. M. Han ◽  
G. L. Hammond
Keyword(s):  
Messenger Rna ◽  
Blot Hybridization ◽  
Late Gestation ◽  
Northern Blot Hybridization ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Mrna Accumulation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pomc Mrna

ABSTRACT Plasma levels of ACTH and cortisol in fetal sheep increase progressively during late pregnancy, providing the stimulus for birth. However, little information is available concerning either sources of pro-opiomelanocortin (POMC, the precursor to ACTH) or changes in POMC gene expression, which may be responsible for the elevated fetal plasma ACTH concentrations. We therefore studied the relative amount of POMC mRNA in fetal sheep hypothalami, anterior pituitaries and adrenals at discrete times of pregnancy between day 60 and term (approximately 145 days) and from newborn lambs. Total RNA from these tissues was analysed by Northern blot hybridization using a human POMC DNA probe, and the amount of POMC mRNA was expressed relative to the signal obtained for 18S ribosomal RNA. A single 1·2 kb transcript was detected by day 60 in the anterior pituitary, and its relative amount did not change significantly until after days 125–130. Pituitary POMC mRNA levels increased significantly at days 138–143, remained elevated at term and increased further in newborn lambs. In contrast, POMC mRNA was undetectable in hypothalami and adrenal glands of fetuses at all ages. The results suggested that the prepartum rise in plasma ACTH concentrations in fetal sheep is due to increased POMC biosynthesis in the fetal pituitary. The increase in POMC mRNA occurs at a time when fetal plasma cortisol concentrations are elevated, indicating that the negative feedback effects of circulating glucocorticoids on the fetal hypothalamicpituitary axis may be obscured by other mechanisms that increase pituitary POMC mRNA accumulation during the last week of gestation. Journal of Endocrinology (1991) 131, 483–489

scholarly journals Fetal Sheep Pituitary Proopiomelanocortin in Late Gestation: Effect of Bilateral Lesions of the Paraventricular Nucleus on Regional and Cellular Messenger Ribonucleic Acid Levels*

Endocrinology ◽  
1997 ◽  
Vol 138 (9) ◽  
pp. 3873-3880 ◽  
Author(s):  
M. E. Bell ◽  
T. R. Myers ◽  
T. J. McDonald ◽  
D. A. Myers
Keyword(s):  
Paraventricular Nucleus ◽  
Gestational Age ◽  
Regional Analysis ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Neurointermediate Lobe ◽  
Cellular Analysis ◽  
Pomc Mrna ◽  
Pituitary Glands

Abstract Previous experiments have clearly indicated that the successful completion of ovine gestation is dependent upon fetal adrenocortical maturation and the associated preterm rise in fetal plasma cortisol. The purposes of this study were to: 1) examine pituitary POMC messenger RNA (mRNA) levels during normal fetal development; and 2) examine the effects of bilateral lesion of the fetal paraventricular nucleus (PVN) on levels and spatial distribution of pituitary POMC mRNA. Pituitary glands were collected from intact fetal sheep of four gestational ages [100–107 days gestational age (dga), n = 8; 117–121 dga, n = 9; 126–130 dga, n = 9; 144–147 dga, n = 8]. Lesions of the PVN (PVN Lx; n = 4) or sham lesions (Sham; n = 5) were performed at 118–122 dga. Pituitary glands from PVN Lx and Sham fetuses were collected at 139–142 dga (term∼ 147 dga). POMC mRNA levels were determined by in situ hybridization. POMC transcript levels were determined by both regional analysis (20× magnification) and analysis of individual corticotropes (400× magnification). There was no difference among gestational age groups in superior anterior pituitary (AP) POMC mRNA levels determined by regional or cellular analysis. POMC mRNA levels were significantly greater in the inferior AP at 144–147 dga, compared with other gestational ages, using regional analysis (P = 0.003) or analysis of individual corticotropes (P &lt; 0.01). POMC mRNA levels in the neurointermediate lobe in 126- to 130-dga fetuses were significantly greater than those in younger fetuses (P = 0.005) but not those in 144- to 147-dga fetuses. There was no difference in POMC mRNA levels in the superior AP between PVN Lx and Sham, using regional analysis or analysis of individual corticotropes. In the inferior AP, there was a significant decrease in POMC mRNA levels in PVN Lx, compared with Sham, using both regional analysis (P &lt; 0.01) and cellular analysis (P &lt; 0.01). There was no difference in POMC mRNA levels in the neurointermediate lobe as the result of bilateral PVN Lx. Our findings support that basal AP POMC mRNA levels are heterogenously distributed in the ovine fetal AP, with POMC mRNA levels in the inferior AP being significantly greater than in superior AP, by 144–147 dga. We further found that the higher POMC mRNA levels in the inferior AP reflect significantly higher corticotrope POMC transcripts and not simply a greater density of corticotropes in this AP region. The increase in POMC mRNA levels at 144–147 dga in the inferior AP seems unrelated to the onset of adrenocortical maturation (at∼ 125–130 dga). Finally, we report that increase in corticotrope POMC transcripts during late gestation in the inferior AP requires an intact PVN.

Dopaminergic regulation of pituitary function in the late-gestation fetal sheep

1996 ◽  
Vol 150 (2) ◽  
pp. 187-194 ◽  
Author(s):  
S G Matthews ◽  
M Fraser ◽  
J R G Challis
Keyword(s):  
Anterior Lobe ◽  
Late Gestation ◽  
Intermediate Lobe ◽  
Mrna Levels ◽  
Amniotic Cavity ◽  
Fetal Sheep ◽  
Pomc Mrna ◽  
Dopaminergic Regulation ◽  
Plasma Prl

Abstract Development of the fetal ovine pituitary is essential for normal maturation and initiation of the parturition process, as well as for orchestrating endocrine responses to stress in utero. Increases in the biosynthesis of ACTH and prolactin (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe (AL) of the pituitary, pro-opiomelanocortin (POMC) biosynthesis and processing are primarily regulated by corticotrophin-releasing hormone and vasopressin. However, POMC in the intermediate lobe (IL) and PRL in the AL are known to be primarily regulated by dopamine, via the D2 receptor, in adult sheep. Because of the importance of ACTH and PRL during gestation we have investigated a potential role of dopamine in the control of both IL melanotrophs and AL lactotrophs and corticotrophs, in late gestation. Catheters were implanted into a maternal femoral artery and vein, fetal carotid artery and jugular vein as well as into the amniotic cavity. At day 130 of gestation, fetuses were infused intravenously with either the specific D2 receptor agonist bromocriptine (n = 5) or vehicle (n=5), for 5 days. Blood samples were taken throughout the experiment and pituitaries were removed at the end of the treatment period. Bromocriptine caused a significant decrease (>50%) in POMC mRNA levels in the IL. In contrast, bromocriptine had no significant effect on POMC mRNA levels or distribution in the AL. Fetal arterial ACTH and cortisol concentrations were unaffected by the bromocriptine infusion, compared with vehicle-infused controls. There was a dramatic decrease (>80%) in plasma PRL concentrations, compared with the control fetuses. However, PRL mRNA levels in the AL were not significantly affected by bromocriptine. In conclusion, we have found that bromocriptine inhibits aspects of both melanotroph and lactotroph function in late-gestation fetal sheep. The data indicate that the fetal pituitary possesses functional D2 receptors in late gestation. Journal of Endocrinology (1996) 150, 187–194

scholarly journals Subpopulations of Corticotrophs in the Sheep Pituitary during Late Gestation: Effects of Development and Placental Restriction

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4762-4771 ◽  
Author(s):  
Kirsten Farrand ◽  
I. Caroline McMillen ◽  
Shigeyasu Tanaka ◽  
Jeffrey Schwartz
Keyword(s):  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pomc Mrna ◽  
Experimental Induction ◽  
Attachment Sites ◽  
Specific Antisera

The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep and may result from an increase in the ratio of ACTH to proopiomelanocortin (POMC) in the fetal circulation. In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH. We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 receptor (CRHR1) shortly before birth and during chronic placental insufficiency. Placental restriction (PR) was induced by removal of the majority of placental attachment sites in five ewes before mating. Pituitaries were collected from control and PR fetal sheep at 140 d (control, n = 4; PR, n = 4) and 144 d (control, n = 6; PR, n = 4). Pituitary sections were labeled with specific antisera raised against POMC, ACTH, and CRHR1. Three major subpopulations of corticotrophs were identified that expressed POMC + ACTH + CRHR1, ACTH + CRHR1, or POMC only. The proportion of pituitary corticotrophs expressing POMC + ACTH + CRHR1 decreased (P &lt; 0.05) between 140 (control, 60 ± 1%; PR, 66 ± 4%) and 144 (control, 45 ± 2%; PR, 56 ± 6%) d. A significantly higher (P &lt; 0.05) proportion of corticotrophs expressed POMC + ACTH + CRHR1 in the pituitary of the PR group compared with controls. This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary that differentially express POMC, ACTH, and CRHR1 and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs.

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