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

Mercer, Julie E.; Clements, Judith A.; Clarke, I. J.; Funder, John W.

doi:10.1159/000125234

Cited by 24 publications

(8 citation statements)

References 23 publications

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“…Indeed, the fact that we could not detect GR-immunoreactivity in the mouse or rat melanotrophs is in agreement with the majority of studies demonstrating the lack of GR (17)(18)(19)(20)(21), and the absence of glucocorticoid effect on either peptide secretion (22), POMC levels (23), or POMC gene expression (24)(25)(26)(27)(28) in the mammalian IL. Nevertheless some effects of glucocorticoids have been reported, but they did not lead to coherent conclusions.…”

Section: Discussionsupporting

confidence: 90%

Glucocorticoids, but not Dopamine, Negatively Regulate the Melanotrophic Activity of the Rabbit Pituitary Intermediate Lobe

Schimchowitsch

Plante

Kienlen

et al. 1994

J Neuroendocrinology

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The leporidae (rabbit and hare) pituitary intermediate lobe (IL) differs from that of other mammals by its neuroendocrine regulation. In particular, it is not submitted to the classic dopaminergic inhibitory control, which has been considered as a repressive factor for the expression of glucocorticoid receptors (GR) in the mammalian IL. Hence, the present experiments aimed at examining the rabbit IL for the possible existence of GR. Using both immunocytochemistry and binding studies with (3H)-dexamethasone, we localized GR in the nuclei of IL cells and showed the presence of saturable and high-affinity type II receptor sites, with Kd approximately 3.9 nM. Also, exposure of cultured IL cells to 10 nM dexamethasone (DEX) resulted in the blockade of melanocyte-stimulating hormone (alpha MSH) secretion stimulated by oxytocin (OT). Importantly, the inhibitory effect was reversed by a 100-fold excess of the glucocorticoid antagonist RU 38486. This is the first study which clearly demonstrates in a mammalian IL, namely the rabbit, the presence of functional GR, involved in the negative regulation of the melanotrophic activity of this gland.

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Section: Discussionsupporting

confidence: 90%

Glucocorticoids, but not Dopamine, Negatively Regulate the Melanotrophic Activity of the Rabbit Pituitary Intermediate Lobe

Schimchowitsch

Plante

Kienlen

et al. 1994

J Neuroendocrinology

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“…The fact that the sheep in experiment I were ovary intact, and those in exper iment 2 were ovariectomized, might be interpreted as possibly influencing ACTH secretory responses. There were, however, no differences in basal ACTH levels between experiments 1 and 2, and recent studies from this laboratory have shown that ovariectomy does not change anterior pituitary POMC mRNA levels in the sheep [26].…”

Section: Discussionmentioning

confidence: 60%

Adrenocorticotropin Responses to Endogenous and Exogenous Secretagogues in the Sheep: Specificity of Glucocorticoid Action

Canny

Clarke

Funder³

1990

Neuroendocrinology

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Glucocorticoids act upon the hypothalamus and pituitary to regulate both corticotropin-releasing factors and adrenocorticotropin (ACTH) in a classical negative feedback loop. There are two distinct receptor systems in the central nervous system for glucocorticoids: type I corticosterone/cortisol-preferring, predominantly hippocampal receptors, and type II dexamethasone-binding receptors with a much broader distribution. To determine the relative roles played by these two receptors in determining basal and stress-induced ACTH/cortisol levels in the sheep, we have conducted two series of experiments. In the first, we infused 4 sheep with cortisol (50 µg/h), or dexamethasone (20 µg/h) for 17 h, collected 10-min blood samples for 3 h for basal hormone levels, and then subjected the sheep to an audiovisual stress (barking dog), 10 µg of ovine corticotropin-releasing factor (oCRF) 1 h later, and 100 U of insulin another 2 h later. Dexamethasone reduced ACTH and cortisol levels, both basal and in response to stress; cortisol infusion had no effect on any parameters; oCRF did not raise ACTH levels. In the second experiment, cortisol (100 µg/h) alone was infused into 4 sheep for 17 h, and blood samples were collected for 3 h for basal hormone levels; this was followed by the injection of 10 µg oCRF, and 2 h later a barking dog was introduced into the sheep shed. Again, cortisol infusion did not affect basal ACTH or cortisol levels, though both cortisol-infused and control animals had ACTH responses to oCRF when it was not preceded by the audiovisual stress. ACTH and cortisol levels were higher in the 2 h following oCRF injection. Subsequent responses to the stress brought on by the dog were not altered. We conclude: (i) with the caveat that cortisol levels did not rise post-infusion, that negative feedback effects of glucocorticoids on the hypothalamo-pituitary adrenal axis in intact sheep are primarily via type II and not type I receptors; (ii) that physiologically induced elevations in cortisol are capable of inhibiting pituitary responsiveness to oCRF in the sheep via an intermediate duration (minutes-to-hours) feedback mechanism, and (iii) that oCRF may play a role in priming the hypothalamo-pituitary-adrenal axis.

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“…In a study of male sheep, testosterone decreased POMC mRNA levels in some, but not all, hypothalamic sites (Hileman et al 1996). In ewes, no difference in anterior pituitary POMC mRNA was reported between intact and GDX animals (Mercer et al 1989), while progesterone and oestradiol treatment appeared to increase anterior pituitary POMC mRNA (Whisnant et al 1992) in GDX ewes. Our present observations may be at odds with a number of studies which report higher ACTH content in the anterior pituitaries of female rats (Lesniewska et al 1990, Chisari et al 1995, though it is not clear if such differences reflect the species studied, or the methodology (mRNA vs peptide content) employed.…”

Section: Discussionmentioning

confidence: 78%

“…Total RNA was extracted from the hemipituitary glands as previously described (Mercer et al 1989) and 25 µg total RNA were run for Northern blotting. The RNA was hybridised with a 32 P-labelled ovine POMC probe (van der Pavert et al 1997).…”

Section: Anterior Pituitary Mrna Assaysmentioning

confidence: 99%

The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep

Canny

O'Farrell²,

Clarke³

et al. 1999

Journal of Endocrinology

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There is a sex difference in the hypothalamo-pituitaryadrenal (HPA) axis of many species, although there are sparse data on the sheep. In the present study we have compared the HPA axes of intact and gonadectomised adult male and female sheep at the level of the median eminence, pituitary and adrenal glands using a variety of in vitro approaches. The concentration of arginine vasopressin (AVP) was higher (P<0·01) in the median eminence of male than female sheep, and was also elevated by gonadectomy of either sex (P<0·01). The concentration of corticotrophin-releasing factor (CRF) in the median eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0·01). Anterior pituitary pro-opiomelanocortin mRNA concentrations were higher (P<0·05) in intact male sheep than in intact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anterior pituitary cells was higher (P<0·05) in cultures derived from female sheep than those from males, but gonadectomy was without effect. There was no effect of sex or gonadectomy on in vitro ACTH secretion in response to AVP, CRF or the combination of AVP and CRF, and in all cases the combination of AVP and CRF generated greater (P<0·0001) ACTH secretion than AVP alone. AVP alone was more effective (P<0·01) than CRF alone as an ACTH secretagogue. The adrenal glands were larger (P<0·05) in female than male sheep, with no effect of gonadectomy. Basal cortisol production was greatest (P<0·05) in cultures of adrenal cells from intact male sheep, though ACTH-and 8BrcAMP-induced cortisol production was greater in the cultures of cells from females (P=0·05); there were no effects of gonadectomy. Cultures of adrenocortical cells from male sheep had greater (P<0·05) basal cAMP production, but ACTH-stimulated cAMP production did not differ between any of the groups of animals. These findings show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity of the axis in the female occurs primarily due to differences at the level of the adrenal gland, and that greater adrenal responsiveness of female animals is due to differences in the latter stages of steroidogenesis, rather than an effect on ACTH signal transduction at its receptor.

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

Cited by 24 publications

References 23 publications

Glucocorticoids, but not Dopamine, Negatively Regulate the Melanotrophic Activity of the Rabbit Pituitary Intermediate Lobe

Glucocorticoids, but not Dopamine, Negatively Regulate the Melanotrophic Activity of the Rabbit Pituitary Intermediate Lobe

Adrenocorticotropin Responses to Endogenous and Exogenous Secretagogues in the Sheep: Specificity of Glucocorticoid Action

The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep

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