Progesterone Receptor, Estrogen Receptor α, and the Type II Glucocorticoid Receptor Are Coexpressed in the Same Neurons of the Ovine Preoptic Area and Arcuate Nucleus: A Triple Immunolabeling Study1

Dufourny, Laurence; Skinner, Donal C.

doi:10.1095/biolreprod.102.005066

Cited by 47 publications

(44 citation statements)

References 78 publications

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“…This is consistent with data in guinea pigs [48], monkeys [49] and rats [50]. As all PR-immunoreactive neurons contain ERα in sheep [36] and rodents [51, 52], it is noteworthy that a fifth of βEND neurons express ERα in the ovine arcuate nucleus [32] but only few (4%) in the rat arcuate nucleus [47]. This is suggestive of a species difference in the steroidal control of opioidergic subpopulations in the arcuate nucleus.…”

Section: Discussionsupporting

confidence: 91%

“…To our knowledge, this is the first study to reveal that nearly a third of the PR-immunoreactive neurons in the ovine arcuate nucleus project to the GnRH-rich regions of the OVLT/preoptic area. Since the majority of estrogen receptor α (ERα) containing neurons also express PR in the arcuate nucleus of the ewe [36], the present data can be considered in context of a recent report showing that approximately 40% of ERα containing neurons in the ovine arcuate nucleus project to the OVLT/preoptic area [39]. It is also noteworthy that a similar percentage of ERα-immunoreactive neurons is reported to project from the arcuate nucleus to the preoptic area in the rat [47].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of triple-labeled neurons FG/PR/βEND or DYNB was determined using software (Adobe Photoshop 7.0, San Jose, Calif., USA), which enables two images taken from the same area to be superimposed. We have previously used this multiple photography approach to study steroid receptor colocalization in the same neurons [36]. To obtain an estimate of the proportion of cells that were either double- or triple-labeled, 36 pairs of photographs were taken from each animal at 20× magnification on 30 sections taken every 200 µm throughout the rostrocaudal extent of the arcuate nucleus.…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…These areas have also been found to express high levels of other neuropeptides, specifically other endogenous opioid peptides, and gonadal steroid receptors (estrogen and progesterone receptors) (33,34). Indeed, the location of OFQ-ir cells in the ovine arcuate nucleus is similar to that of dynorphin (35,36), neurokinin B (37), enkephalin (38), ␤-endorphin (36), dopamine (39), and neuropeptide Y (39).…”

Section: Discussionmentioning

confidence: 99%

Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

et al. 2007

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Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. O RPHANIN FQ (OFQ), also known as nociceptin, is a member of the family of endogenous opioid peptides, which also includes ␤-endorphin, enkephalins, and dynorphin (1). Whereas sharing some homology with dynorphin, OFQ does not exhibit appreciable binding affinity for classical opioid receptors (1, 2); rather it functions as an endogenous ligand for the opioid receptor like (ORL)-1 receptor (1). OFQ cells are present in the preoptic area, anterior hypothalamus, and arcuate nucleus of the hypothalamus of the rat (3) and human (4). Functionally, OFQ has been implicated in a variety of systems including pain (5), anxiety (6), cardiovascular function (7), food intake (8), circadian rhythms (9), and cognition (10). There is also evidence that OFQ may play a role in neuroendocrine function: intracerebroventricular delivery of OFQ in the rat stimulates GH and prolactin (11, 12) and has been reported to both stimulate (13) and inhibit (14) corticosterone secretion. Sinchak et al. (15) have shown that OFQ delivered into the ventromedial nucleus facilitates lordosis in female rats in a dose-dependent manner. However, there has been relatively little attention to the possible role of OFQ in reproductive neuroendocrine function, specifically in the control of GnRH secretion.GnRH neurons, and their projections to the median eminence, control the secretion of pituitary LH and thus comprise the final common pathway for the neuroendocrine control of reproduction (16). Endogenous opioid peptides are important regulators of the GnRH system, controlling both the preovulatory surge (17) and pulsatile secretion (18) of GnRH. OFQ has been shown to inhibit forskolin-induced GnRH secretion in a dose-dependent manner from rat hypothalamic fragments (19). OFQ cells in the preoptic area and anterior hypothalamus overlap the site of a majority of GnRH perikarya (20 -22). In addition, OFQ fibers and ORL-1 receptors are present in high abund...

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“…It is noteworthy that NPY terminals have been shown to synapse on GnRH perikarya in the sheep [33]. Moreover, as we have shown that most ERα-expressing cells colocalize with PR [34] and that a significant population of NPY-immunoreactive neurons in the arcuate express ERα [35], it is probable that this population will also be targeted by progesterone.…”

Section: Introductionmentioning

confidence: 99%

Progesterone-Receptive Dopaminergic and Neuropeptide Y Neurons Project from the Arcuate Nucleus to Gonadotropin-Releasing Hormone-Rich Regions of the Ovine Preoptic Area

Dufourny

Caraty

Clarke³

et al. 2005

Neuroendocrinology

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Progesterone inhibits gonadotropin-releasing hormone (GnRH) secretion in sheep through an interneuronal system located in the mediobasal hypothalamus. This study focused on known inhibitors of GnRH secretion in sheep, dopamine and neuropeptide Y (NPY). As the distributions of tyrosine hydroxylase (TH)- and NPY-immunoreactive neurons overlap with progesterone receptors (PR) in the arcuate nucleus, we hypothesized that, if these neurons mediate, at least partially, the inhibitory feedback signal of progesterone, then they should co-express PRs. Fluorogold (FG), a retrograde tracer, was injected into the preoptic area of ovariectomized ewes pretreated with estrogen and progesterone. When the FG injection site encompassed at least 80 GnRH neurons, sections from the arcuate nucleus were processed using dual immunocytochemistry for PR and either TH or NPY. We found that 30% of PR-immunoreactive, 12% of TH-containing and 21% of NPY-synthesizing neurons project toward this GnRH-rich region. Of the PR/TH dual-labeled cells, which represent 21% of PR and 31% of TH cells, respectively, 22% displayed FG labeling. Of the PR/NPY neurons, which account for 19% of PR and 67% of NPY neurons, respectively, 26% were FG fluorescent. This study suggests that subsets of arcuate nucleus dopaminergic and NPY neurons may transduce, at least in part, the progesterone-mediated inhibition of GnRH secretion.

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Progesterone Receptor, Estrogen Receptor α, and the Type II Glucocorticoid Receptor Are Coexpressed in the Same Neurons of the Ovine Preoptic Area and Arcuate Nucleus: A Triple Immunolabeling Study1

Cited by 47 publications

References 78 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

Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Progesterone-Receptive Dopaminergic and Neuropeptide Y Neurons Project from the Arcuate Nucleus to Gonadotropin-Releasing Hormone-Rich Regions of the Ovine Preoptic Area

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