Changes in glucocorticoid receptor mRNA in the developing ovine pituitary and the effects of exogenous cortisol

1995 ◽  
Vol 144 (3) ◽  
pp. 483-490 ◽  
Author(s):  
S G Matthews ◽  
K Yang ◽  
J R G Challis

Abstract Developmental changes in pituitary glucocorticoid receptor (GR) mRNA were examined during gestation and early neonatal life using in situ hybridization. Pituitaries were harvested from sheep fetuses at days 60–80, 100–120, 130–135, 140–142 and term, and from lambs of days 0–7 and 30–60, and adults. GR mRNA was present in the pars distalis by day 60, levels increased through gestation, and there was a redistribution of GR mRNA, resulting in a relatively greater abundance at the base of the pars distalis. At term, there was a significant (P<0·05 compared with the day 140–142 fetuses) elevation of GR mRNA, which was maintained in the newborn lamb, reaching highest levels at days 30–60 of neonatal life. GR mRNA was undetectable in the pars intermedia until day 120, but subsequently increased to high levels at term. Interestingly, the expression of GR mRNA in the pars intermedia dropped precipitously in the newborn (P<0·05 compared with term), though levels recovered in the older lambs and adults. The regional and cellular distribution of GR mRNA correlated closely with the presence of immuno-reactive GR (irGR) in the pituitary; the majority of irGR was present in the nuclei. Intrafetal infusion of cortisol (12 h; 5 μg/min) in late gestation (day 135) had no effect on GR mRNA expression in either the pars distalis or pars intermedia. These results indicated that, in the fetal pituitary, (1) the GR gene is expressed in both the pars distalis and pars intermedia, (2) levels of GR mRNA in the fetal pituitary correlated with the distribution of nuclear irGR, (3) GR mRNA is present at higher levels in the inferior aspect of the pars distalis, its abundance increases immediately prior to parturition and is maintained in the newborn, and (4) cortisol infusion for 12 h does not affect GR mRNA in either region of the pituitary, suggesting that, in the short term, glucocorticoids do not directly regulate GR synthesis. Journal of Endocrinology (1995) 144, 483–490

1994 ◽  
Vol 13 (2) ◽  
pp. 175-185 ◽  
Author(s):  
S G Matthews ◽  
X Han ◽  
F Lu ◽  
J R G Challis

ABSTRACT Ontogenic changes in pituitary pro-opiomelanocortin (POMC) mRNA and prolactin (PRL) mRNA were examined during gestation and early neonatal life using in situ hybridization histochemistry. Pituitaries were harvested from fetuses at days 60–80, 100–120, 135–140 and 142–143 of gestation and at term, and from lambs at days 1–7 and 30–60 of age and adults. POMC mRNA, present by day 60, rose during mid- and late gestation. Concurrently there was a change in corticotroph distribution, resulting in a relatively greater quantity of POMC mRNA at the base of the pars distalis. At term, there was a significant (P<0·05) further elevation of POMC mRNA. POMC mRNA levels remained high in the newborn lamb but decreased in the adult. Cells in the pars intermedia expressed large amounts of POMC mRNA early in fetal life and this pattern persisted throughout gestation and into the neonatal period. Changes in the expression of the POMC gene correlated closely with the presence of immunoreactive (ir)ACTH in the pituitary; in fetuses the proportion of irACTH-positive cells rose to 10% of pars distalis cells by day 100 and did not change significantly thereafter. The lactotrophs contained PRL mRNA by day 60, and the quantity increased towards parturition (P<0·05). PRL mRNA subsequently decreased in the neonate, but rose as the lamb matured. These results indicate that in the fetal pituitary: (1) the POMC gene is highly expressed during gestation in both the pars distalis and the pars intermedia, (2) changes in the amounts of POMC mRNA and PRL mRNA in the pars distalis correlate with the distribution of irACTH and irPRL respectively, and (3) POMC mRNA is distributed primarily in the inferior aspect of the pars distalis, and in this region its quantity is highest immediately prior to parturition.


1995 ◽  
Vol 14 (1) ◽  
pp. 109-116 ◽  
Author(s):  
K Yang ◽  
S G Matthews ◽  
J R G Challis

ABSTRACT To examine the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in the control of glucocorticoid actions in the ovine pituitary during development, we have sought developmental changes in the distribution and the level of 11β-HSD1 mRNA by in situ hybridization. In the pars distalis, 11β-HSD1 mRNA was present by day 60; its amount did not change significantly until term (days 145–147) when it increased dramatically. The level of 11β-HSD1 mRNA increased further during the postnatal period. In contrast, 11β-HSD1 mRNA in the pars intermedia was not detectable until day 135; it increased in amount at days 140–143, but did not change significantly thereafter through to adulthood. We have also measured levels of both dehydrogenase and reductase activities of 11β-HSD1 in the pars distalis of fetal sheep at day 140 and term, and of postnatal sheep at 1–2 months of age, to determine whether changes in 11β-HSD1 mRNA are reflected in the levels of enzyme activities. There were progressive increases in both dehydrogenase and reductase activities from day 140 to 1–2 months postnatally, although dehydrogenase activity was consistently higher than reductase activity. Finally, we have determined the effect of short-term intrafetal cortisol infusion (5 μg/min for 12 h) on levels of pituitary 11β-HSD1 mRNA by in situ hybridization. There was no effect of cortisol infusion on 11β-HSD1 mRNA expression. The present results demonstrate that 11β-HSD mRNA and enzyme activity in the pars distalis of fetal sheep increase dramatically at term when plasma levels of both ACTH and cortisol are elevated. This suggests that 11β-HSD1 may contribute to the proposed resetting of cortisol negative feedback within the fetal pituitary at that time.


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


1988 ◽  
Vol 85 (23) ◽  
pp. 9331-9335 ◽  
Author(s):  
M. Aronsson ◽  
K. Fuxe ◽  
Y. Dong ◽  
L. F. Agnati ◽  
S. Okret ◽  
...  

1995 ◽  
Vol 268 (6) ◽  
pp. E1096-E1107 ◽  
Author(s):  
S. G. Matthews ◽  
J. R. Challis

Developmental changes in the abundance, localization, and distribution of corticotropin-releasing hormone (CRH) mRNA and arginine vasopressin (AVP) mRNA in the ovine hypothalamus were examined by in situ hybridization. The effects of fetal hypoxemia in the presence or absence of concomitant cortisol in late gestation (day 135) were also investigated. CRH and AVP mRNA were present at low levels within the paraventricular nucleus (PVN) and AVP mRNA was present in the supraoptic nucleus (SON) by day 60 (full term = 147 days). During late gestation, there were increases (P < 0.05, days 140–143 vs. days 100–120) in CRH mRNA, a further increase (P < 0.05, full term vs. days 140–143) at full term (fetuses delivered in active labor), and a subsequent decline postpartum (compared with full term). AVP mRNA in the magnocellular PVN increased (P < 0.05) in late gestation, levels did not change in parvocellular fields compared with full term fetuses, but magnocellular and parvocellular AVP mRNA increased in the newborn (P < 0.05, newborn vs. full term). AVP mRNA in the SON showed a developmental profile similar to that of the PVN, although there was an increase earlier in gestation (P < 0.05, days 100–120 vs. days 60–80). Hypoxemia caused increases (P < 0.05) in CRH mRNA, plasma adrenocorticotropic hormone, and cortisol concentrations, and although magnocellular and parvocellular AVP mRNA appeared elevated, changes just failed to attain significance. Cortisol infusion attenuated the hypoxemia-induced increase in CRH mRNA and adrenocorticotropic hormone but was without effect on basal CRH mRNA levels.


2002 ◽  
Vol 282 (3) ◽  
pp. E721-E732 ◽  
Author(s):  
Christopher S. Kovacs ◽  
Linda L. Chafe ◽  
Mandy L. Woodland ◽  
Kirsten R. McDonald ◽  
Neva J. Fudge ◽  
...  

The expression of calcitropic genes and proteins was localized within murine placenta during late gestation (the time frame of active calcium transfer) with an analysis of several gene-deletion mouse models by immunohistochemistry and in situ hybridization. Parathyroid hormone-related protein (PTHrP), the PTH/PTHrP receptor, calcium receptor, calbindin-D9k, Ca2+-ATPase, and vitamin D receptor were all highly expressed in a localized structure of the murine placenta, the intraplacental yolk sac, compared with trophoblasts. In the PTHrP gene-deleted or Pthrp-null placenta in which placental calcium transfer is decreased, calbindin-D9k expression was downregulated in the intraplacental yolk sac but not in the trophoblasts. These observations indicated that the intraplacental yolk sac contains calcium transfer and calcium-sensing capability and that it is a probable route of maternal-fetal calcium exchange in the mouse.


1972 ◽  
Vol 50 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Johan A. Hellebust ◽  
Arne Haug

Amino acids, particularly alanine and aspartate, become more strongly labeled than mannitol in short-term 14C-photoassimilation experiments. The amino acids are the most likely sources of carbon for alginic acid synthesis and respiration in the dark, in contrast to mannitol, which appears to be relatively unavailable. Temperature is very important in determining the rate of loss of recent photoassimilate in L. digitata. The rate of photosynthesis, on a fresh weight basis, is much higher for blades than for stipes.The time course for incorporation of photoassimilated carbon into alginate differs for the stipe and blade both in light and dark periods. Very little 14C enters alginate in blades in the dark, while alginate in stipes acquires considerable amounts of activity during dark periods. Alginate in both blade and stipe acquires 14C predominantly in mannuronic acid residues of their alginate during short-term photoassimilation periods, while guluronic acid residues become relatively more rapidly labeled during dark periods.


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