Ultrastructure of neurons in the ventromedial nucleus or the hypothalamus in ovariectomized rats with or without estrogen treatment

Cohen, Rochelle S.; Pfaff, Donald W.

doi:10.1007/bf00219357

Cited by 109 publications

(34 citation statements)

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“…E 2 can modulate dendrite morphogenesis and induce synaptogenesis in hypothalamic (8)(9)(10)(11) and extrahypothalamic neuronal populations (12,13), and such structural plasticity may mediate E 2 feedback effects (14). That the ER␣ isoform appears to mediate many of these effects rapidly (15) is consistent with the idea that membrane-initiated, nonclassical ER␣ signaling can rapidly induce the actin-cytoskeletal reorganization required for synaptic remodeling (16).…”

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confidence: 60%

“…Because ER␣ signaling and PAKs can both mediate rapid actin cytoskeletal organization and morphological plasticity (11,23,(48)(49)(50)(51), it is thus possible that these downstream cellular events comprise a major route by which E 2 -activated PAKs may mediate negative feedback control over GnRH and, hence, LH secretion. It remains to be determined whether such a rapid, PAK-mediated alteration in cell connectivity functions in this manner and, if so, which of the many known PAK substrates (e.g., actin-related protein 2/3 complex, filamin, and/or cofilin) (19) may mediate these actions.…”

Section: Discussionmentioning

confidence: 99%

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p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis

Zhao

Park

McDevitt

et al. 2009

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

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Nonclassical estrogen receptor ␣ (ER␣) signaling can mediate E2 negative feedback actions in the reproductive axis; however, downstream pathways conveying these effects remain unclear. These studies tested the hypothesis that p21-activated kinase 1 (PAK1), a serine/threonine kinase rapidly activated by E 2 in nonneural cells, functions as a downstream node for E 2 signaling pathways in cells of the preoptic area, and it may thereby mediate E 2 negative feedback effects. Treatment of ovariectomized (OVX) rats with estradiol benzoate (EB) caused rapid and transient induction of phosphorylated PAK1 immunoreactivity in the medial preoptic nucleus (MPN) but not the arcuate nucleus. To determine whether rapid induction of PAK phosphorylation by E 2 is mediated by nonclassical [estrogen response element (ERE)-independent] ER␣ signaling, we used female ER␣ null (ER␣ ؊/؊ ) mice possessing an ER knock-in mutation (E207A/G208A; AA), in which the mutant ER␣ is incapable of binding DNA and can signal only through membrane-initiated or ERE-independent genotropic pathways (ER␣ ؊/AA mice). After 1-h EB treatment, the number of pPAK1-immunoreactive cells in the MPN was increased in both wild-type (ER␣ ؉/؉ ) and ER␣ ؊/AA mice but was unchanged in ER␣ ؊/؊ mice. Serum luteinizing hormone (LH) was likewise suppressed within 1 h after EB treatment in ER␣ ؉/؉ and ER␣ ؊/AA but not ER␣ ؊/ ؊ mice. In OVX rats, 5-min intracerebroventricular infusion of a PAK inhibitor peptide but not control peptide blocked rapid EB suppression of LH secretion. Taken together, our findings implicate PAK1 activation subsequent to nonclassical ER␣ signaling as an important component of the negative feedback actions of E 2 in the brain.GnRH ͉ LH ͉ estrogen receptor ␣ O varian estradiol-17␤ (E 2 ) conveys negative feedback actions within the reproductive axis that include inhibition of gonadotropin-releasing hormone (GnRH) neurosecretion and suppression of gonadotrope responsiveness to GnRH stimulation. Both actions can be sustained by E 2 treatment regimens that maintain serum E 2 levels in low physiological ranges (1) and they can also be manifested rapidly, within minutes after E 2 injection (2). Studies of estrogen receptor ␣ (ER␣), ER␤, and ER␣/␤ null mutant mice have clearly implicated ER␣ as the isoform essential for E 2 negative feedback regulation in vivo (3, 4).Cell signaling pathways that transduce ER␣-mediated negative feedback are not well understood. In classical ER␣ signaling mechanisms, E 2 binds nuclear ERs and recruits coactivators to consensus palindromic estrogen response elements (EREs). Direct binding of ERs to EREs thereby mediates alterations in transcription of target genes. Nonclassical ER␣ signaling mechanisms operate independently of ER␣ binding directly to EREs and include protein-protein interactions with transcription factors, such as AP1, SP1, and NF-B (5), which in turn mediate transcriptional regulation at their cognate response elements. Nonclassical ER␣ signaling also includes membrane-associated receptor activation coupled...

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confidence: 60%

Section: Discussionmentioning

confidence: 99%

p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis

Zhao

Park

McDevitt

et al. 2009

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

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“…The earliest estrogen effect is the increase of transcription of ribosomal RNA, 13 followed rapidly by morphological effects, including those in the nucleolus itself 14 and a striking elaboration of rough endoplasmic reticulum in the cytoplasm. 15 Catherine Woolley 16 and her colleagues have shown, probably consequent to the phenomena above, a stimulatory effect of estrogen treatment on dendritic growth. In the female rat hypothalamus, Maya Frankfurt 17 and Lori Flanagan 18,19 have reported that estrogens foster dendritic growth and an increased number of synapses.…”

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confidence: 98%

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Mong

Pfaff

2004

Mol Psychiatry

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Genes induced by estrogens in the mammalian forebrain influence a variety of neural functions. Among them, reproductive behavior mechanisms are very well understood. Their functional genomics provide a theoretical paradigm for linking genes to neural circuits to behavior. We propose that estrogen-induced genes are organized in modules: Growth of hypothalamic neurons; Amplification of the estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex behavior circuitry; and Synchronization of mating behavior with ovulation. These modules may represent mechanistic routes for CNS management of successful reproduction. Moreover, new microarray results add estrogen-dependent genes, including some expressed in glia, suggesting possible hormone-dependent neuronal/ glial coordination. Molecular Psychiatry (2004) 9, 550-556. doi:10.1038/sj.mp.4001493Keywords: sex; estrogen; gene; hypothalamus; lordosis; arousal; noradrenalin; acetylcholine; oxytocin; enkephalin; opioid; GnRH; LHRH; neurotrophic; anxiety Sexual behaviors are important for psychiatry. Not only hypersexual disorders but also concerns about lack of sexual desire are prominent, internationally, in the psychiatric landscape. Further, in some traditions of psychiatric theory, sexual problems are held to be at the root of apparently unrelated syndromes. Finally, biological thought has held that sexual affiliations provide the bauplan, the structural precedent, for a wide variety of other social relations, both normal or abnormal. Fortunately, the molecular analysis of stereotyped sexual behaviors has benefited greatly from several strategic advantages: Even in mammals, simple stimuli and responses permit neural net analysis. Steroid hormones acting through nuclear receptors which are transcription factors invoke regulated gene expression, for example, in hypothalamic neurons.1 In turn, these neurons control mating behavior circuits.Drawing hormone-regulated gene expression into the explanation of mammalian sex behavior has proceeded rapidly. Here we theoretically propose a gene network-really, a micronet-downstream of estrogen action in the forebrain responsible for courtship and lordosis behavior in females. Not a massive review of the literature or an original data report, this paper comprises an attempt to draw different transcriptional systems into a new theoretical formulation. These efforts to explain hormone-driven behaviors have benefited from Rosenfeld's example of genetic network control over pituitary gland development.2 Both direct and indirect causal routes are depicted below.Causal routes, downstream from genomic action; a modular system emergent The primary sex behavior of female quadrupeds, lordosis, depends on defined physical signals: cutaneous stimuli and estrogens þ progestins 1 (E þ P). The neural circuit has been worked out; estrogen-dependent transcription in ventromedial hypothalamic cells allows permissive signals to the midbrain central gray, thus enabling the rest of the circuit. In the absence of fear or anxiety-pro...

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“…Both rat ventromedial nucleus (of unknown steroid receptor content) and the ER-containing VL cells of the guinea-pig contain large stacks of Golgi cisternae, Nissl bodies (stacks of rough endoplasmic reticulum) with ribbon formations, and multivesicular bodies. Since the occurrence of the 'ribbons' and extent of the stacking of the endoplasmic reticulum may be dependent on hormone status in this (35) and other brain regions (c.g. 45), the ER-immunoreactivc neurons of the intact guinea-pig may contain substantially more ribboned rough endoplasmic reticulum than viewed here in our ovariectomized animals.…”

Section: Figmentioning

confidence: 99%

Ultrastructural Characteristics of Estrogen Receptor‐Containing Neurons of the Ventrolateral Nucleus of the Guinea‐Pig Hypothalamus

Silverman

DonCarlos

Morrell

1991

J Neuroendocrinology

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The ventrolateral nucleus of the hypothalamus (VL) of the guinea-pig is a key cell group in the neural circuitry underlying the estrogen-dependent lordosis reflex. The extent to which neurons in the VL are responsive to estrogen or to synaptic inputs depends in part on the presence of specific estrogen and neurotransmitter receptors within the target cells. It also depends on the number, type and location of synaptic inputs. In addition, both sensitivity to circulating hormones and transmitter responsiveness show estrogen-inducible alterations in the VL. To understand more about the cell types that are directly modulated by estrogens via the nuclear steroid binding protein and the synaptic connectivity of these neurons, we have carried out an ultrastructural study of estrogen receptor-containing cells in the VL of the female guinea-pig.Estrogen receptor was localized for both light and electron microscopy using a specific monoclonal antibody, H-222, directed against the human estrogen receptor. Numerous immunoreactive neurons were found in the VL. These cells had simple, relatively smooth dendritic processes that were generally unbranched. Reaction product was most intense in the nucleus; lighter deposits were seen in some but not all somata and proximal dendrites. No cell was observed with only cytoplasmic staining. At the ultrastructural level, this distribution of reaction product within cells was confirmed. Gold deposits were associated with euchromatin and excluded from the nucleolus, nucleolar-associated heterochromatin and Barr body. In the cytoplasm, the small aggregates of gold particles were randomly distributed. Two types of cytologically distinct immunoreactive neurons were characterized. The most numerous category was of large cells with extensive rough endoplasmic reticulum, frequently organized as whorls or ribbons, Several stacks of Golgi cisterna, numerous mitochondria and multivesicular bodies. A smaller population, representing approximately 5% of the total, was of much smaller cells which had only a thin rim of cytoplasm around the nucleus, scattered elements Of the rough endoplasmic reticulum and a single small Golgi saccule. Based on size, we suggest that the larger neurons are Projection neurons and that the smaller ones form local circuits. The larger cells received a dense axo-somatic and axo-dendritic innervation. Most of the presynaptic terminals contained small, clear round vesicles; synaptic densities on either pre-or postsynaptic side were absent though a well defined synaptic cleft was evident. Very few synapses were found on the small cells even when serial sections were examined. It is clear that the larger, estrogen receptor-containing neurons are in a position to integrate both hormonal and neuronal signals and to transmit this information to other regions of the central nervous system involved in the outflow of reproductive behaviors.The cnordination of physiology and behavior essential to SUCessful reproduction requires the molecular interaction of gonadal sterolcis a...

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Ultrastructure of neurons in the ventromedial nucleus or the hypothalamus in ovariectomized rats with or without estrogen treatment

Cited by 109 publications

References 34 publications

p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis

p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Ultrastructural Characteristics of Estrogen Receptor‐Containing Neurons of the Ventrolateral Nucleus of the Guinea‐Pig Hypothalamus

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