Distribution of Fos Immunoreactivity in the Lamina Terminalis and Hypothalamus Induced by Centrally Administered Relaxin in Conscious Rats

McKinley, MJ; Burns, Peta; Colvill, L M; Oldfield, Brian J.; Wade, John D.; Weisinger, R. S.; Tregear, Geoffrey W.

doi:10.1046/j.1365-2826.1997.00600.x

Cited by 61 publications

(41 citation statements)

References 3 publications

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“…Previous studies found that acute intracerebroventricular (icv) (33) or intravenous (iv) administration of RLX to rats (59) increased Fos-immunoreactivity (IR) in neurons in the SFO, organum vasculosum of the lamina terminalis, supraoptic nucleus (SON), and paraventricular nucleus of the hypothalamus (PVN), consistent with RLX-induced activation of forebrain volume regulation pathways. Some of the activated (Fos-IR) magnocellular neurons in the SON and PVN were also immunopositive for AVP or oxytocin, although the extent of activation was not quantified (33).…”

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Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Coldren

Brown

Hasser

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Coldren KM, Brown R, Hasser EM, Heesch CM. Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats. Am J Physiol Regul Integr Comp Physiol 309: R1553-R1568, 2015. First published September 23, 2015; doi:10.1152/ajpregu.00186.2015.-Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptordenervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 Ϯ 3%) and mean arterial pressure (MAP; 26 Ϯ 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml Ϫ1 ·h Ϫ1 ; 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 Ϯ 2%) and arginine-vasopressin (AVP)-IR (21 Ϯ 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy.Fos; paraventricular nucleus; subfornical organ; circumventricular organs; ANG II; arginine-vasopressin WITH ITS HIGHEST CIRCULATING levels achieved during pregnancy, relaxin (RLX) is a 6-kDa peptide hormone secreted primarily by the corpus luteum of the ovary. RLX-2 in humans is functionally equivalent to RLX-1 in all other mammals, and often both are called simply "relaxin" (2, 4, 21). Although best known for its role in growth and remodeling of the female reproductive tract during pregnancy, RLX peptide and RLX binding sites are present in male reproductive tissue and the heart, vasculature, kidney, and brain of both males and females. In regards to the cardiovascular system, in both male and female humans and rats, chronic administration of RLX causes vascular remodeling, angiogenesis, and systemic vasodilation (8). Endogenous RLX is a major contributor to peripheral vasodilation and augmented renal function seen in pregnancy, and recent clinical trials suggest that exogenously administered RLX may have therapeutic value in treating heart-failure patients (2,8,14).In addition to peripheral vascular effects, circulating RLX plays an important role in the central nervous sys...

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confidence: 74%

“…Some of the activated (Fos-IR) magnocellular neurons in the SON and PVN were also immunopositive for AVP or oxytocin, although the extent of activation was not quantified (33).…”

mentioning

confidence: 99%

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Coldren

Brown

Hasser

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Published studies have suggested that relaxin receptors may not be evenly distributed in these areas. Central administration of relaxin in conscious rats produces Fos-like immunoreactivity (Fos-LI) in neurons scattered around the most rostral, dorsal and lateral parts of SFO but not in its central caudal zone; while in the OVLT, the neurons exhibiting Fos-LI were situated in its dorsal pole and a few neurons in the central vascular zone and at the lateral edges (McKinley et al, 1997). Assuming that only these neurons expressed relaxin receptors, it would require higher resolution receptor autoradiography for proper characterization.…”

Section: Discussionmentioning

confidence: 99%

“…Relaxin also has direct e ects on nonreproductive tissues and produces powerful chronotropic and inotropic responses in rat isolated atria (Kakouris et al, 1993), participates in the regulation of blood pressure (Mumford et al, 1989;Parry et al, 1990) and¯uid balance (Weisinger et al, 1993), and releases vasopressin and oxytocin (Dayanithi et al, 1987;Way & Leng, 1992) by activating the neurosecretory magnocellular hypothalamic nuclei (Oshero & Phillips, 1991;McKinley et al, 1997). These e ects may relate to some of the physiological changes observed in females during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment

Tan

Wade

Tregear

et al. 1999

British J Pharmacology

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1 The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [ 33 P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. 2 The binding kinetics of [ 33 P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+18C) and dissociated slowly. The association and dissociation rate constants were 4.31+0.34610 8 M 71 min 71 and 1.55+0.38610 73 min 71 respectively. Thus, the kinetic dissociation constant was 3.46+0.59 pM. 3 Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding a nities (pK D ) of [ 33 P]-human gene 2 relaxin (B33) were 8.92+0.09 in atrial myocardium and 8.79+0.04 in cerebral cortex of male rats, and 8.79+0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in nonreproductive tissues. 4 In male rats, treatment with 17b-oestradiol (20 mg in 0.1 ml sesame oil s.c., 18 ± 24 h) signi®cantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no signi®cant e ect in atria and cerebral cortex, but it signi®cantly increased the density of relaxin receptors in uterine myometrium. 5 Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+0.02), and cerebral cortex (8.90+0.03) and uterine myometrium (8.89+0.03) with a nities not signi®cantly di erent from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with a nities (8.35+0.09 in atria, 8.22+0.07 in cerebral cortex and 8.48+0.06 in uterine myometrium) signi®cantly less than human gene 2 (B33) and porcine relaxins. 6 Quantitative receptor autoradiography is the method of choice for measurement of a nities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17b-Oestradiol treatment produced complex e ects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no e ect on the atria and cerebral cortex of the female rats.

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“…Evidence of this influence is presented in reports that the intracerebroventricular (i.c.v.) (1) injection of relaxin results in stimulation of oxytocin and vasopressin secretion, water drinking, and a pressor response (3)(4)(5)(6)(7)(8). i.c.v.…”

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confidence: 99%

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat

Sunn

Egli

Burazin

et al. 2002

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

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Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 g͞h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxininduced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10 ؊7 M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10 ؊7 M angiotensin II. The data indicate that bloodborne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.R elaxin is a peptide hormone secreted by the corpus luteum of the ovary during pregnancy. Relaxin acts on reproductive tissues such as the pubic symphysis, uterus, and cervix (1, 2), but it may also influence the brain (3). Evidence of this influence is presented in reports that the intracerebroventricular (i.c.v.) (1) injection of relaxin results in stimulation of oxytocin and vasopressin secretion, water drinking, and a pressor response (3-8). i.c.v. administration of relaxin also stimulates increased expression of c-fos in groups of neurons in the supraoptic nucleus (SON) and hypothalamic paraventricular nucleus (PVN), as well as in the subfornical organ (SFO), median preoptic nucleus (MnPO), and organum vasculosum of the lamina terminalis (OVLT) (9). Circulating relaxin probably has endocrine actions on the brain, because high-affinity-binding sites for relaxin are present in the SFO and OVLT of the rat (10), two brain regions that are accessible to circulating relaxin because they lack a blood-brain barrier (11). Also, i.v. infusion of relaxin causes vasopressin secretion and water drinking in the rat, effects that may be mediated through brain angiotensinergic mechanisms (12,13). Evidence that relaxin [together with other hormones such as angiotensin II (Ang II) and vasopressin] plays a physiological role in regulating body fluid homeostasis d...

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Distribution of Fos Immunoreactivity in the Lamina Terminalis and Hypothalamus Induced by Centrally Administered Relaxin in Conscious Rats

Cited by 61 publications

References 3 publications

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat

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