Localization of estrogen-receptive neurons projecting to the GnRH neuron-containing rostral preoptic area of the ewe.

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Abstract

Estrogen exerts important feedback effects upon the biosynthetic and secretory behavior of gonadotropin-releasing hormone (GnRH) neurons to control reproductive functioning. The mechanism of estrogen action upon these neurons is unclear and seems likely to involve the transsynaptic regulation of GnRH neurons. The objective of the present study was to identify the estrogen-receptive neural populations which project to the general vicinity of the GnRH perikarya in the rostral preoptic area and diagonal band of Broca (rPOA/DBB) of the ewe. Intact breeding-season ewes received an injection of the retrograde tracer fluorogold (FG) into the rPOA/DBB, and their hypothalami and brainstems examined for the presence of FG and estrogen receptor alpha (ERalpha) immunocytochemistry. Retrogradely labeled neurons were identified principally within the lateral septum (LS), lamina terminalis, bed nucleus of the stria terminalis, POA, arcuate nucleus (ARN), ventromedial nucleus (VMN) and median eminence. Smaller numbers of FG-immonoreactive cells were found in the caudal brainstem where they resided mostly in the ventrolateral medulla (VLM). Dual-labeled cells exhibiting both FG and ERalpha staining were prominent in the POA, LS and at all rostrocaudal levels of the VMN and ARN. Small numbers of dual-labeled cells were found in the VLM. These observations indicate that a number of distinct ERalpha-expressing neural populations project to the rPOA/DBB where the majority of the GnRH perikarya are found in the ewe. Although it is not possible to determine the direct connectivity of these projections with GnRH neurons, the findings provide an initial neuroanatomical framework through which the transsynaptic actions of estrogen on ovine GnRH neurons may be tested.

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Involvement of GABA in the feedback action of estradiol on gonadotropin and prolactin release: hypothalamic GABA and catecholamine turnover rates.

T Mansky, P Mestres-Ventura, W. Wuttke (1982)

The concentrations and turnover rates of norepinephrine (NE), dopamine (DA) and gamma-aminobutyric acid (GABA) were measured in discrete brain areas of diestrous (D), proestrous (P), ovariectomized (OVX) and ovariectomized rats treated with estradiol-benzoate (EB) 12 or 24 h before decapitation. The turnover of NE in the medial preoptic area (MPO) correlates well with plasma LH levels under all endocrine conditions showing high NE turnover in P and OVX and low NE turnover in D and OVX-EB animals. The DA turnover shows no hormone-dependent changes in the MPO. In those animals where estrogens exert no (OVX) or a negative feedback action (D, OVX-EB) on LH the GABA turnover correlates inversely with LH and preoptic NE turnover showing low GABA turnover values in OVX and high values in D and OVX-EB. For P animals the inverse correlation cannot be confirmed. It is concluded that GABA mediates the negative feedback action of estrogens to LH-RH perikarya located in the MPO. GABA might act by presynaptic inhibition of NE axon terminals. This hypothesis is supported by morphological findings which indicate that axon terminals in the MPO are in close contact without separating glial lamellae. In the anterior mediobasal hypothalamus (AMBH) NE turnover correlates best with serum prolactin levels being high in P and OVX animals 24 h after EB treatment. The DA turnover is increased in OVX rats 24 h after EB. It is not yet clear if this increase might be a consequence of the elevated prolactin levels. GABA turnover in the AMBH shows no significant changes. GABA concentrations and turnover rates were also determined in the mediocortical amygdala where estrogen receptors have been reported and in the nucleus accumbens. No significant changes could be observed in these regions.

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Estrogen Receptor Expression in Brainstem Noradrenergic Neurons of the Sheep

Sharon Simonian, Bernadette Delaleu, Alain Caraty … (1998)

Noradrenergic neurons are implicated in the estrogen-dependent neural regulation of luteinizing hormone secretion in a variety of mammalian species. The current study has used immunocytochemical methods to determine whether estrogen receptors (ER) are expressed within the brainstem of the ewe and to establish their relationship to noradrenergic neurons. Using a monoclonal mouse antiserum directed against the N-terminal of ERα, four distinct populations of ERα-immunoreactive cells were identified in ovine medulla and pons. The largest population was found in the superficial laminae of the spinal nucleus of the trigeminal nerve, followed by the nucleus tractus solitarius, lateral area postrema, and ventrolateral medulla. Double-labelling immunocytochemistry using antisera directed against the ERα and dopamine-β-hydroxylase revealed that noradrenergic neurons expressing ER immunoreactivity were only found in ventrolateral medulla (A1 cell group) and nucleus tractus solitarius (A2 cell group). No double-labelled cells were identified in the A5, A6, or A7 noradrenergic cell groups. ERs were expressed with a clear rostrocaudal topography within the A1 and A2 populations, with 80–90% of noradrenergic neurons expressing ERα in the caudalmost medulla as compared with less than 5% rostral to the obex. Our findings demonstrate that, as in the rat, the ovine A1 and A2 neurons express ERs in a defined topographical manner, while, dissimilar to the rat, ERα is not synthesized by noradrenergic neurons in the other cell groups. These observations indicate that A1 and A2 noradrenergic neurons in the ovine brainstem are likely to be influenced by circulating estrogens and lay the neuroanatomical foundations for investigating the functional role of these cell populations within the gonadotropin-releasing hormone neuron network of the sheep.