Estrogen Induces Ultrastructural Changes in Progesterone Receptor-Containing GABA Neurons of the Primate Hypothalamus

Leranth, Csaba; Shanabrough, Marya; Naftolin, Frederick

doi:10.1159/000125962

Cited by 52 publications

(32 citation statements)

References 22 publications

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“…6b) in PR-immunoreactive cells of OVX monkeys. Similar structures have been ob served in the cytoplasm of a subpopulation of rat [26] and primate [41] hypothalamic GABAergic neurons following OVX + estrogen treatment or after OVX alone.…”

Section: Discussionmentioning

confidence: 57%

“…6b). A detailed description and statistical analysis on the OVX and OVX plus estrogen treatment resulted changes of nemato somes and whorl bodies in PR-containing neurons of the primate hypothalamus has been published previously by our laboratory [41], In the neuropil surrounding the PRcontaining cells of estrogen-treated animals, axon termi- nal boutons were found that contained 'clumped' syn aptic vesicles. Many of these boutons synapsed with PR-containing neurons ( fig.…”

Section: Resultsmentioning

confidence: 99%

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Transmitter Content and Afferent Connections of Estrogen-Sensitive Progestin Receptor-Containing Neurons in the Primate Hypothalamus

Léránth

MacLusky²,

Brown³

et al. 1992

Neuroendocrinology

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Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotrans-mitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypotha-lamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.

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Section: Discussionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Transmitter Content and Afferent Connections of Estrogen-Sensitive Progestin Receptor-Containing Neurons in the Primate Hypothalamus

Léránth

MacLusky²,

Brown³

et al. 1992

Neuroendocrinology

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“…A recent study suggests that glutamatergic neurons of the pubertal female monkey express both estrogen and progesterone receptors [7], implying that progesterone regulates LHRH release by acting directly on glutamatergic neurons. Moreover, immunocytochemical studies have demonstrated that GABA neurons contain progesterone receptors [7][8][9], and that GABAergic neurons innervate glutamatergic neurons in the monkey hypothalamus [29]. It is, therefore, also possible that progesterone regulates glutamatergic neurons through GABA receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms involved in the progesterone-enhanced LH surge in estrogenprimed animals seem to include not only an increase in sensitivity to LH-releasing hormone (LHRH) at the pituitary [3] but also LHRH release at the hypothalamic level [4]. Because monoaminergic [5,6], amino acidergic [7][8][9] and peptidergic neurons [6,10] contain progesterone receptors whereas few LHRH neurons do [6], circulating progesterone might be sensed by non-LHRH neurons. …”

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confidence: 99%

Increase in In Vivo Glutamate Release in the Mediobasal Hypothalamus During Progesterone-Enhanced LH Surge in Estrogen-Primed Ovariectomized Rats.

Murahashi

Nagatani

Maeda

et al. 1998

Journal of Reproduction and Development

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Abstract. Progesterone has a facilitating effect on luteinizing hormone (LH) surges induced by estrogen in ovariectomized (OVX) rats. The aim of the present study was to elucidate the involvement of excitatory amino acids such as glutamate and aspartate, and noradrenaline (NA) in the mediobasal hypothalamus/median eminence (MBH) region in a progesterone-enhanced LH surge. Ovariectomized animals were implanted with a Silastic tubing containing crystalline estradiol (E 2 ) for 2 days, and some of them received sc injection of progesterone (4 mg) at 0900 h on the day of sampling. The MBH was perfused using the push-pull perfusion method to determine the levels of glutamate, aspartate, glycine, glutamine, and NA during the LH surge. Blood samples were collected through an atrial cannula to determine plasma LH levels. In animals treated with both E 2 and progesterone, levels of glutamate and glutamine significantly (P<0.01) increased simultaneously 1 to 2 h before the peak of LH surge, whereas those levels did not significantly change by E 2 treatment alone. Levels of aspartate, glycine and NA showed no significant changes during steroid(s)-induced LH surges. These results suggest that the facilitating effect of progesterone on estrogen-induced LH surges might be mediated, at least in part, by glutamate released at the MBH where the majority of LHRH nerve terminals are distributed. Key words: LH surge, Progesterone, Glutamate, Estrogen, Push-pull perfusion.(J. Reprod. Dev. 44: [135][136][137][138][139][140] 1998) Excitatory amino acids (EAAs) have been suggested as one candidate to mediate the facilitating effect of progesterone on LHRH release. For example, Brann et al. have revealed that administration of EAA antagonists blocks progesterone-induced LH surges in estradiol (E 2 )-primed ovariectomized (OVX) rats [11,12]. Moreover, the release of glutamate and aspartate in the preoptic area (POA) is increased during progesterone-induced LH surges in E 2 -treated OVX rats [13]. We hypothesized that the facilitating effect of progesterone on an estrogen-induced LH surge may be mediated by EAAs released not only at the POA but also at the mediobasal hypothalamus/ median eminence (MBH) region, where the majorrogesterone has a facilitating effect on estrogen-induced luteinizing hormone (LH) surges P in female rats [1,2]. The mechanisms involved in the progesterone-enhanced LH surge in estrogenprimed animals seem to include not only an increase in sensitivity to LH-releasing hormone (LHRH) at the pituitary [3] but also LHRH release at the hypothalamic level [4]. Because monoaminergic [5,6], amino acidergic [7][8][9] and peptidergic neurons [6,10] contain progesterone receptors whereas few LHRH neurons do [6], circulating progesterone might be sensed by non-LHRH neurons.

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“…One candidate neurotransmitter that may convey estradiol signals to GnRH neurons is GABA, which provides a major synaptic input to GnRH neurons (Leranth et al, 1985b;Jansen et al, 2003;Pompolo et al, 2003). Hypothalamic GABAergic cells express ER␣ (Flugge et al, 1986;Leranth et al, 1991) and GnRH neurons express GABA A receptors (GABA A Rs) that are synaptically activated (Sim et al, 2000;Sullivan et al, 2003). GABA A R activation can inhibit or excite a cell depending on intracellular chloride levels (Kaila, 1994;Rivera et al, 1999) and membrane voltage.…”

Section: Introductionmentioning

confidence: 99%

Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

Christian¹,

Moenter²

2007

J. Neurosci.

125

114

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Ovulation is initiated by a surge of gonadotropin-releasing hormone (GnRH) secretion by the brain. GnRH is normally under negative feedback control by ovarian steroids. During sustained exposure to estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of this steroid switches to positive, inducing the surge. Here, we used an established ovariectomized, estradiol-treated (OVXϩE) mouse model exhibiting daily surges to investigate the neurobiological mechanisms underlying this switch. Specifically, we examined changes in GABA transmission to GnRH neurons, which can be excited by GABA A receptor activation. Spontaneous GABAergic postsynaptic currents (PSCs) were recorded in GnRH neurons from OVXϩE and OVX mice in coronal and sagittal slices. There were no diurnal changes in PSC frequency in cells from OVX mice in either slice orientation. In OVXϩE cells in both orientations, PSC frequency was low during negative feedback but increased at surge onset. During the surge peak, this increase subsided in coronal slices but persisted in sagittal slices. Comparison of PSCs before and during tetrodotoxin (TTX) treatment showed TTX decreased PSC frequency in OVXϩE cells in sagittal slices, but not coronal slices. This indicates estradiol acts on multiple GABAergic afferent populations to increase transmission through both activity-dependent and -independent mechanisms. Estradiol also increased PSC amplitude during the surge. Estradiol and the diurnal cycle thus interact to induce shifts in both GABA transmission and postsynaptic response that would produce appropriate changes in GnRH neuron firing activity and hormone release.

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Estrogen Induces Ultrastructural Changes in Progesterone Receptor-Containing GABA Neurons of the Primate Hypothalamus

Cited by 52 publications

References 22 publications

Transmitter Content and Afferent Connections of Estrogen-Sensitive Progestin Receptor-Containing Neurons in the Primate Hypothalamus

Transmitter Content and Afferent Connections of Estrogen-Sensitive Progestin Receptor-Containing Neurons in the Primate Hypothalamus

Increase in In Vivo Glutamate Release in the Mediobasal Hypothalamus During Progesterone-Enhanced LH Surge in Estrogen-Primed Ovariectomized Rats.

Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

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