Immunocytochemical Localization of Beta Endorphin and Gonadal Steroid Regulation of Proopiomelanocortin Messenger Ribonucleic Acid in the Ewe

Whisnant, Scott; Curto, Karen A.; Rl, Goodman

doi:10.1159/000126311

Cited by 32 publications

(21 citation statements)

References 41 publications

(64 reference statements)

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“…βEND neurons were only detected in the arcuate nucleus and the subventricular division of the arcuate nucleus, which lies immediately above the median eminence of the ewe as previously reported [41]. This distribution overlaps the reported distribution of PR-immunoreactive cells [33] and double-labeled neurons were observed throughout the nucleus.…”

Section: Resultssupporting

confidence: 86%

Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area

Dufourny¹,

Caraty²,

Clarke³

et al. 2005

Neuroendocrinology

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Progesterone inhibits gonadotropin-releasing hormone (GnRH) secretion through interneuronal systems located in the mediobasal hypothalamus in ewes. Endogenous opioid peptides are implicated in this inhibition of GnRH secretion. The distributions of endogenous opioid peptides are known to overlap with progesterone receptors (PR) in the arcuate nucleus. We investigated whether PR is expressed by β-endorphin and dynorphin B neurons in the arcuate nucleus and if a subset of double-labeled cells projects to the preoptic area where most GnRH neurons are detected. Injection of a retrograde tracer, Fluorogold, into the rostral preoptic area was performed in ovariectomized ewes pretreated with estrogen and progesterone. Brain sections were processed using double immunocytochemistry. Only brains of ewes with an injection site encompassing at least 80 GnRH neurons were processed for PR and then either β-endorphin or dynorphin B immunocytochemistry. Antigen retrieval is essential for PR detection but causes Fluorogold to fade. Thus, quantitative analysis was performed on photographs taken before and after antigen retrieval. We found that 25–30% of PR-containing neurons, 20% of β-endorphin cells and 22% of dynorphin B neurons in the arcuate nucleus project toward the preoptic area. From the PR/β-endorphin double-labeled cells that represent 25 and 36% of PR and β-endorphin cells, respectively, 35% were labeled with Fluorogold. From the PR/dynorphin B double-labeled cells that account for 39 and 62% of PR and dynorphin B neurons, respectively, 26% contained Fluorogold. These data strongly support the hypothesis that progesterone acts in the arcuate nucleus through β-endorphin and dynorphin B neurons to affect preoptic area GnRH neurons.

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Section: Resultssupporting

confidence: 86%

Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area

Dufourny¹,

Caraty²,

Clarke³

et al. 2005

Neuroendocrinology

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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%

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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“…This suggests that an interneuronal system(s) must transmit P's effects to the GnRH neurons. Although the noradrenergic and GABAergic systems are putative candidates (10), the strongest evidence implicates the opioidergic system (9,10,(56)(57)(58)(59). Indeed, anatomical studies in rats (60,61) and monkeys (62) suggest a direct action of opiates on GnRH neurons, which could explain the rapid transduction of P's effects.…”

Section: Discussionmentioning

confidence: 99%

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Skinner

Evans

Delaleu

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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145

122

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Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0-12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12-24 hr, P implant removed; 24-36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3␣-hydroxy-5␣-pregnan-20-one, which operates through the type A ␥-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system. Progesterone (P) is the dominant ovarian steroid present in the peripheral circulation during the mammalian reproductive cycle and serves a number of important regulatory roles. The luteal phase elevation in P inhibits pulsatile gonadotropinreleasing hormone (GnRH) and luteinizing hormone (LH) secretion (1-4) and prevents the occurrence of GnRH (5) and LH (6, 7) surges in response to fluctuations in peripheral estrogen (E) levels that accompany the waves of follicular growth occurring in the ovary (8). We have also recently demonstrated that the luteal phase elevation of P affects both the timing of the LH surge relative to E stimulation and the magnitude of the coincident GnRH surge (D.C.S., N.P.E., and A.C., unpublished results). Despite its obvious importance in regulating reproduction, little is known about how and where P acts to powerfully inhibit the neuroendocrine reproductive axis.Our first study, using the hypophyseal portal cannulation approach, assessed directly the timing of the changes in GnRH secretion that follow both an abrupt decrease and an increase in circulating P concentrations. To avoid potential P-E interactions, short-term ovariectomized (OVX) ewes were used.Since P modulates tonic LH secretion by affecting GnRH pulse frequency (1-4), it is held that P acts through neural targets and putative candidates include the opioidergic, noradrenergic, and ␥-aminobutyric acid (GABA) systems (9, 10). The p...

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Immunocytochemical Localization of Beta Endorphin and Gonadal Steroid Regulation of Proopiomelanocortin Messenger Ribonucleic Acid in the Ewe

Cited by 32 publications

References 41 publications

Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area

Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area

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

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

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