Angiotensin II AT1A receptor mRNA expression is induced by estrogen-progesterone in dopaminergic neurons of the female rat arcuate nucleus (original) (raw)
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Brain Research, 2006
The expression of angiotensin II (Ang II) receptors in the brain is modulated by estradiol and progesterone. Considering that Ang II plays a critical role in controlling prolactin secretion and that neurons in the arcuate nucleus (ARC) are the main regulator of this function, the present study aimed to evaluate ARC Ang II receptor binding in 2 experimental models with different estradiol and progesterone plasma levels. Animals were divided into 4 groups: ovariectomy (OVX) plus oil vehicle, OVX plus estradiol and progesterone replacement, lactating rats on day 7 postpartum, and lactating rats on day 20. Animals were killed by decapitation, and the brains were removed. Ang II receptors were quantified by autoradiography in ARC. Trunk blood samples were collected, and plasma estradiol and progesterone were measured by radioimmunoassay. Treatment of OVX rats with estradiol and progesterone increased Ang II receptor binding when compared to OVX vehicle-treated animals. Plasma estradiol (r = +0.77) and progesterone (r = +0.87) were highly correlated with Ang II receptors in ovariectomized animals. Lactating rats (day 20) showed a significant decrease in Ang II receptor binding and plasma progesterone when compared to lactating rats (day 7), however, no difference was seen in plasma estradiol. Plasma levels of progesterone (r = +0.81), but not estradiol (r = +0.32), were highly correlated with Ang II receptors in lactating rats. In conclusion, present results show that ARC Ang II receptors decreases on day 20 of lactation compared to day 7 and are highly correlated with plasma progesterone, indicating a pivotal role for progesterone in this regulation.
Neuropeptides, 1998
This study determined the effect of the selective angiotensin II (A II) AT 1 receptor subtype antagonist Iosartan in the medial preoptic area (MPOA) of ovariectomized rats, treated with estrogen or untreated, on the release of gonadotropins (LH and FSH) and prolactin (PRL). The MPOA is sensitive to the action of A II and contains cell bodies of neurons producing luteinizing hormone-releasing hormone and a large density of estradiol receptors. Plasma FSH was not altered in any situation. However, Iosartan blocked and estradiol facilitated the stimulating and inhibitory effects of A II microinjection into the MPOA on LH and PRL secretion, respectively. The results indicate that these effects are mediated by AT1 receptors in the MPOA and that estradiol may modulate them. On the other hand, Iosartan itself reduced LH secretion in ovariectomized rats, indicating that the increase in the secretion of this hormone, after removal of the negative feedback caused by estradiol, is due, at least in part, to the action of A II on AT~ receptors of the MPOA.
Brain Research, 2005
Angiotensin II (Ang II) receptors in specific brain areas and in the anterior pituitary are controlled by reproductive hormones. Since Ang II also plays a role in controlling reproductive functions, such as luteinizing hormone and prolactin secretion, the objective of the present study was to evaluate the regulation of Ang II receptors by estradiol (E 2 ) and progesterone (P) in areas of the brain involved in homeostatic and reproductive functions, such as the locus coeruleus (LC), median preoptic nucleus (MnPO) and subfornical organ (SFO). Adult female rats were ovariectomized under anesthesia and divided into 2 groups after 2 weeks: OVX plus E 2 /P replacement (OVXE 2 P) and OVX plus oil vehicle (OVX). E 2 was injected for 3 consecutive days followed by an injection of P on the 4th day. Animals were killed by decapitation and the brains were removed and frozen. Consecutive coronal brain sections were cut in a cryostat and Ang II receptors were quantified by autoradiography in the MnPO, LC and SFO. Treatment of OVX rats with E 2 and P induced a significant increase in the Ang II receptor binding (fmol/mg protein) in the MnPO (OVX: 4.48 T 0.58 and OVXE 2 P: 9.89 T 1.65), LC (OVX: 2.72 T 0.37 and OVXE 2 P: 8.03 T 0.9) and SFO (OVX: 5.45 T 0.66 and OVXE 2 P: 10.73 T 1.79) compared to OVX animals treated with the vehicle, P < 0.05. In conclusion, these results show that Ang II receptors are upregulated by E 2 and P in the LC, MnPO and SFO of ovariectomized rats. D
Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia
AJP: Endocrinology and Metabolism, 2004
Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. Th...
Peptides, 1997
Angiotensin II (AII)-containing neurons with cell bodies in the rostral medial hypothalamus and axons project to the external layer of the median eminence, so that AII maybe released into the hypophyseal portal vessels for actions on the pituitary gland. Indeed, intrahypothalamic actions of the peptide on the release of hypothalamic hormones and direct actions on the pituitary have been reported. To determine the role of endogenously released AII in hypothalamic-pituitary hormone release, we have determined the effects of central immunoneutralization of AII upon the plasma concentrations of prolactin (PRL), growth hormone (GH), thyroidstimulating hormone (TSH), and adrenocorticotropic hormone (ACTH). Specific antiserum directed against AII (AB-AII) or normal rabbit serum (NRS), as a control, was microinjected into third ventricular (3V) cannulae of conscious, ovariectomized (OVX) rats. Immediately before and at various intervals after this procedure, blood samples were withdrawn through previously implanted external jugular catheters. Three hours after injection of the AB-AII, plasma PRL levels diverged from those of the NRS-injected animals and progressively increased from 4 to 24 h after administration of the antiserum. Results were similar with respect to plasma GH, except that the increase in the AB-AII animals above that in the NRS-injected controls from 4 to 6 h was not significant, but was highly significant on measurement 24 h after injection, at which time plasma GH was three times higher than in control rats. Similarly, following injection of AB-AII, plasma TSH values did not diverge significantly from those of the NRS-injected controls until 3 h after injection. From 3 to 5 h they remained constant and significantly elevated above values in the NRS-injected controls with a further nonsignificant increase at 6 h. At 24 h, there was no longer a difference between the values in both groups. In contrast to the significant elevations in plasma hormone levels observed with respect to PRL, GH, and TSH following injection of the antiserum, there was no change in plasma ACTH between the AB-AII-injected and NRS-injected animals throughout the same period of observation. Previous results by others have shown that intraventricular injection of AII has a suppressive action on the release of PRL, GH, and TSH. Consequently, we believe that the antiserum is acting intrahypothalamically to block the action of AII within the hypothalamus, resulting in the elevation of the three hormones mentioned. Therefore, the AII neurons appear to have a physiologically significant suppressive action on the release of hypothalamic neurohormones controlling the release of PRL, GH, and TSH. In contrast, there apparently is no effect of intrahypothalamically released AII on the secretion of corticotropin-releasing factors under these nonstress conditions. We cannot rule out an action of the antiserum at the pituitary level; however, in view of the fact that the actions of AII directly on the gland are to stimulate PRL, GH, TSH, and ACTH release, it appears that the antiserum was acting at the hypothalamic level.
Actions of angiotensin II and dopamine in the medial preoptic area on prolactin secretion
Physiological research / Academia Scientiarum Bohemoslovaca
Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectomized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of DA antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and DA actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of DA through D 2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of DA through D 1 receptors and in other part by inhibition of stimulatory action of DA through D 2 receptors.
Estrogen upregulates renal angiotensin II AT1 and AT2 receptors in the rat
Regulatory Peptides, 2005
We studied renal AT 1 and AT 2 receptors in male, female, ovariectomized and ovariectomized-estrogen-treated Wistar-Hanover and Wistar-Kyoto rats. AT 1 receptors and AT 1A receptor mRNA predominated, with no significant differences between males and females. AT 2 receptor expression was restricted in female rats to the capsule, the transition zone between outer and inner medulla, the endothelium lining the papilla, and arcuate arteries and veins. There were no AT 2 receptors in male rats, while male mice express substantial numbers of estrogen-dependent AT 2 receptors. Arcuate arteries and veins expressed AT 1B mRNA in males and females, and AT 2 mRNA in females only. AT 1 receptor and AT 2 receptor expression were estrogen-dependent, with increases in AT 1 and AT 2 receptor expression after estrogen treatment in ovariectomized rats. Estrogen treatment increased prostaglandin E 2 (PGE 2) and cGMP concentrations in the renal medulla, and eNOS expression in cortical arteries. In rodents, expression of renal Angiotensin II receptor types is estrogen-dependent, with significant species, strain and area differences. Our results support an important role for AT 2 receptors in the regulation of renal function and in the protective effects of estrogen in the kidney.
Journal of the renin-angiotensin-aldosterone system : JRAAS, 2007
Objective. Considering the controversial data regarding the role of the brain renin-angiotensin system (RAS) on the thirst and sodium appetite in ovariectomised rats, we aimed to evaluate the role of the brain angiotensin II (Ang II) AT 1-receptor on the nocturnal fluids intake. Materials and methods. Groups of Wistar female rats were ovariectomised and chronically given oestrogen or vehicle to evaluate its influence on effects induced by i.c.v. injection of losartan,Ang I and Ang II. Results. The i.c.v. losartan decreased basal water intake in the ovariectomised group.Ang II but not Ang I-induced nocturnal dipsogenic and natriorexigenic responses in ovariectomised rats. In oestrogen-treated rats, both peptides increased fluids intake. Previously, i.c.v. losartan abolished these effects in all groups. Oestrogen replacement decreased the nocturnal fluids intake, attenuated the losartan and Ang II effects, and highlighted the Ang I response. Conclusions. The present study has shown for the first time the involvement of AT 1-receptor in regulating nocturnal basal water and salt intake in ovariectomised rats. In addition, our data have revealed an unexpected increased brain Ang Imediated fluid intake in oestrogen-treated ovariectomised compared to ovariectomised rats, which was blocked by previous i.c.v. losartan. Our data have therefore shown that oestrogen influences homeostatic behaviours dependent on brain RAS.
Brain Research, 2009
The physiological actions of brain Angiotensin II AT 2 receptors and their relationship to Angiotensin II AT 1 receptors remain controversial. To further clarify their role, we determined to what extent systemic administration of an AT 2 receptor antagonist affected AT 2 receptor binding within the brain and the expression of AT 1 receptors. For this purpose, we subcutaneously administered the AT 2 receptor antagonist PD123319 (1 mg/kg/day) to adult male rats for two weeks via osmotic minipumps. We also studied the content of pituitary adrenocorticotropic hormone and vasopressin, representative of hypothalamic-pituitary-adrenal axis activation, and the tyrosine hydroxylase gene expression in the locus coeruleus as a measure of central norepinephrine function. We found significant decreases in AT 2 receptor binding in brain areas inside the blood brain barrier, the inferior olive and the locus coeruleus. AT 2 receptor blockade increased AT 1 receptor binding and mRNA expression not only in the subfornical organ and the median eminence, situated outside the blood brain barrier, but also in the hypothalamic paraventricular nucleus, located inside the blood brain barrier. These changes paralleled decreased expression of tyrosine hydroxylase mRNA in the locus coeruleus and decreased pituitary adrenocorticotropic and vasopressin content. Our results demonstrate that sustained peripheral administration of an AT 2 antagonist decreases binding to brain AT 2 receptors, indicating that this drug is a useful tool for the study of their central role. AT 2 receptor activity inhibition up-regulates AT 1 receptor expression in specific brain areas. Blockade of brain AT 2 receptors is compatible with enhanced hypothalamic-pituitary-adrenal axis and decreased central sympathetic system activity.
Biology of Reproduction, 2000
In target tissues of most mammalian and avian species, progesterone receptors (PR) are expressed as structurally related, but functionally distinct, isoforms A and B, and they are regulated by estrogen (E) as well as by their cognate ligand, progesterone (P 4). The objectives of the present work were to identify mRNA expression for the A and B isoforms of PR in the anterior pituitary of the rat, to examine its regulation by gonadal steroids, and to compare this regulation with that in the primary target organ, the uterus. Messenger RNAs for the PR isoforms, determined by two separate reverse transcription-polymerase chain reaction protocols, one that detects PR A and PR B equally and the other specific for PR B, were identified in anterior pituitary of female and male rats. In anterior pituitary of cycling female rats, steady-state mRNA levels for both PR A؉B and PR B were highest at 0900 h on proestrus, declined rapidly to nadir values at 0900 h on metestrus (PR A؉B) or 0900 h on estrus (PR B), and remained below proestrous values through 2100 h on diestrus. Administration of E to intact proestrous female rats caused significant increases in mRNA for both PR A؉B and PR B on estrus and metestrus. Blockade of P 4 action by administration of the antiprogestins RU-486 and ZK-98299 on proestrus had no effect on PR mRNA levels on the morning of estrus. Ovariectomy two and ten days after surgery markedly reduced mRNA levels for both PR A؉B and PR B. Whereas treatment of 10-day-ovariectomized rats with E led to marked induction of mRNA for PR A؉B and PR B two days later, treatment with P 4 one day after treatment had no effect on basal or E-stimulated PR mRNA. Regulation of PR mRNA expression in the pituitary differed from that in the uterus, in which P 4 treatment of ovariectomized rats antagonized the E-induced rise in mRNA for PR B, and antiprogestins increased mRNA for both isoforms. In addition to induction of PR mRNA in the pituitary of female rats by E in vivo, we also demonstrated induction by E in primary culture of anterior pituitary cells in vitro. We conclude that in the anterior pituitary of female rats, both the A and B isoforms of PR are expressed and regulated by E.