Alpha‐Oestrogen and Progestin Receptor Expression in the Hypothalamus and Preoptic Area Dopaminergic Neurones During Oestrous in Cycling Rats

Leite, Cristiane Mota; Szawka, Raphael E.; Anselmo-Franci, Janete Aparecida

doi:10.1111/j.1365-2826.2007.01624.x

Cited by 13 publications

(18 citation statements)

References 62 publications

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“…However, whether E 2 modulates the effect of kisspeptin on the activity of TIDA neuronal terminals and whether the response of males to kisspeptin is E 2 ‐dependent remained to be clarified. Because E 2 is a major regulator of TIDA neurones , we postulated that E 2 might modulate the responsiveness of TIDA neurones to kisspeptin in both sexes. We therefore investigated the effects of Kp‐10 on the activity of neuroendocrine dopaminergic neurones and PRL secretion and determined the role of E 2 in this mechanism.…”

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confidence: 99%

Kisspeptin Regulates Tuberoinfundibular Dopaminergic Neurones and Prolactin Secretion in an Oestradiol‐Dependent Manner in Male and Female Rats

Ribeiro

Leite

Kalil

et al. 2015

J Neuroendocrinology

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Prolactin (PRL) secretion is inhibited by hypothalamic dopamine. Kisspeptin controls luteinising hormone (LH) secretion and is also involved in PRL regulation. We further investigated the effect of kisspeptin-10 (Kp-10) on the activity of tuberoinfundibular dopaminergic (TIDA) neurones and the role of oestradiol (E2 ) in this mechanism. Female and male rats were injected with i.c.v. Kp-10 and evaluated for PRL release and the activity of dopamine terminals in the median eminence (ME) and neurointermediate lobe of the pituitary (NIL). Kp-10 at the doses of 0.6 and 3 nmol increased plasma PRL and decreased 4-dihydroxyphenylacetic acid (DOPAC) levels in the ME and NIL of ovariectomised (OVX), E2 -treated rats but had no effect in OVX. In gonad-intact males, 3 nmol Kp-10 increased PRL secretion and decreased DOPAC levels in the ME but not in the NIL. Castrated males treated with either testosterone or E2 also displayed increased PRL secretion and reduced ME DOPAC in response to Kp-10, whereas castrated rats receiving oil or dihydrotestosterone were unresponsive. By contrast, the LH response to Kp-10 was not E2 -dependent in either females or males. Additionally, immunohistochemical double-labelling demonstrated that TIDA neurones of male rats contain oestrogen receptor (ER)-α, with a higher proportion of neurones expressing ERα than in dioestrous females. The dopaminergic neurones of periventricular hypothalamic nucleus displayed much lower ERα expression. Thus, TIDA neurones express ERα in male and female rats, and kisspeptin increases PRL secretion through inhibition of TIDA neurones in an E2 -dependent manner in both sexes. These findings provide new evidence about the role of kisspeptin in the regulation of dopamine and PRL.

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Kisspeptin Regulates Tuberoinfundibular Dopaminergic Neurones and Prolactin Secretion in an Oestradiol‐Dependent Manner in Male and Female Rats

Ribeiro

Leite

Kalil

et al. 2015

J Neuroendocrinology

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“…The number of TH‐ and FRA/TH‐ir neurones was quantified bilaterally in the in the Pe (16 sections), rostral (R‐ARC; 4 sections), middle (16 sections) and caudal (C‐ARC; 6 sections ) regions of the ARC. The middle region of the ARC was further divided into dorsomedial (DM‐ARC) and ventrolateral (VL‐ARC) subpopulations by a line forming a 50° angle with the horizontal plane in the midline (21). Data are expressed as the percentage of TH‐ir neurones coexpressing FRA and the number of TH‐ir neurones per section.…”

Section: Methodsmentioning

confidence: 99%

“…The amplitude of oestrous surge is approximately half of the pro‐oestrous one (29, 30). In addition, we have recently demonstrated that expression of ERα and PR in dopaminergic neurones of the ARC and Pe vary during oestrus, despite unchanged plasma levels of ovarian steroids (21). Fos‐related antigen (FRA) expression in dopaminergic neurones of the ARC and Pe has been reported to decrease by the time of prolactin surge on pro‐oestrus (31).…”

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Activity of Hypothalamic Dopaminergic Neurones During the Day of Oestrus: Involvement in Prolactin Secretion

Leite

Ribeiro

Szawka

et al. 2010

J Neuroendocrinology

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A secretory surge of prolactin occurs on the afternoon of oestrus in cycling rats. Pituitary prolactin is inhibited by dopamine. We evaluated the activity of the neuroendocrine dopaminergic neurones during oestrus and dioestrus, as determined by dopaminergic activity in the median eminence and neurointermediate lobe of the pituitary, as well as Fos-related antigen expression in tyrosine hydroxylase (TH)-immunoreactive (ir) neurones of the arcuate nucleus (ARC) and periventricular nucleus (Pe). During oestrus, the 4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence decreased at 16.00 h, coinciding with the increase in plasma prolactin levels. Similarly, the expression of Fos-related antigen in TH-ir neurones of Pe and rostral-, dorsomedial- and caudal-ARC also decreased at 16.00 h. On dioestrus, 4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence and Fos-related antigen expression in TH-ir neurones of Pe and rostral-ARC decreased at 18.00 h, whereas prolactin levels were unaltered. No variation in dopaminergic activity was found in the neurointermediate lobe of the pituitary on either oestrus or dioestrus. The number of TH-ir neurones in the ARC and parameters of dopaminergic activity were found to be generally lower on oestrus compared to dioestrus. The transitory decrease in the activity of neuroendocrine dopaminergic neurones temporally associated with the prolactin surge on the afternoon of oestrus suggests a role for dopamine in the generation of the oestrous prolactin surge.

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“…Oestradiol (E 2 ) is a major endocrine factor participating in control of prolactin secretion in female rats, via the αER (oestrogen receptor) and dopaminergic pathways in the pre‐optic area of the hypothalamus , independent of circadian rhythm (e.g. modulates magnitude rather than timing; ).…”

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Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

Brott

Werkheiser

Campbell

et al. 2012

Basic Clin Pharma Tox

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Centrally acting dopamine agonists (e.g. bromocriptine) and dopamine transport inhibitors (e.g. GBR12909) are known to inhibit oestradiol-induced prolactin release. The capacity of peripherally restricted compounds to do likewise, however, is unknown. Here, the effects of the peripherally restricted dopamine receptor agonist carmoxirole on oestradiol-induced prolactin release were investigated. Dual-cannulated ovariectomized rats were used, so that a robust, reproducible response to exogenous oestrogen could be induced and sequential blood samples were taken with minimal stress. Carmoxirole (15 mg/kg) inhibited oestradiol-induced prolactin release, similar to bromocriptine and GBR12909. However, carmoxirole also induced a rapid, transient, oestradiol-independent release of prolactin. These data show that peripherally restricted dopamine receptor agonists are sufficient to inhibit oestradiol-induced prolactin release. Like centrally acting compounds, they may therefore be expected to affect the incidence of prolactin-dependent tumours in rat carcinogenesis studies without inducing central-mediated side effects.Understanding the relevance or translation of pre-clinical drug effects to the clinic is critical for accurate human risk assessment for new pharmaceutical agents. In particular, accurate identification of specific mechanisms of serious toxicities observed in non-clinical species, and translation of specific mechanism in human beings can provide a scientific basis with which to evaluate specific risk in human beings. For example, it is known that some endocrine modulators can affect the incidence of particular tumours in life-time rat carcinogenicity bioassays, but not in human beings [1]. More specifically, the centrally active dopamine (D2) receptor agonist, bromocriptine, can induce hypoprolactinaemia in rats and human beings, but increases the incidence of hyperplastic proliferative endometrial lesions and benign and malignant uterine tumours only in rats [2], which has been postulated to be due to a lesser impact of prolactin on ovarian steroidogenesis in human beings [3].Prolactin is a peptide hormone spontaneously produced and secreted by lactotrophs in the anterior lobe of the pituitary gland under control by hypothalamic factors. In the rat, three dopaminergic systems [tuberoinfundibular (TIDA), tuberohypophyseal and periventricular hypophyseal dopaminergic neurons] regulate prolactin release, with the relative contribution varying between reproductive, physiological and pathological stages [4]. Hypothalamic dopaminergic neurons play a central role in the regulation of prolactin release by exerting an effect on the lactotrophs via the D2 receptor [5,6]. However, dopamine can also affect prolactin secretion by acting in the hypothalamus [7,8]. The pituitary lactotroph population is not entirely homogenous; mammosomatotropes, which are particularly common in neonatal rats, are differentiated into lactotrophs under the influence by oestrogens and secrete both prolactin and growth hormone [9]...

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Alpha‐Oestrogen and Progestin Receptor Expression in the Hypothalamus and Preoptic Area Dopaminergic Neurones During Oestrous in Cycling Rats

Cited by 13 publications

References 62 publications

Kisspeptin Regulates Tuberoinfundibular Dopaminergic Neurones and Prolactin Secretion in an Oestradiol‐Dependent Manner in Male and Female Rats

Kisspeptin Regulates Tuberoinfundibular Dopaminergic Neurones and Prolactin Secretion in an Oestradiol‐Dependent Manner in Male and Female Rats

Activity of Hypothalamic Dopaminergic Neurones During the Day of Oestrus: Involvement in Prolactin Secretion

Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

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