Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats

Arai, Yasumasa; Sekine, Y.; Murakami, Shigeyuki

doi:10.1016/0168-0102(96)01070-x

Cited by 154 publications

(67 citation statements)

References 22 publications

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“…The molecular cascades leading to Baxdependent cell death in these regions likely differ, however. SNB cell survival is androgen dependent (Breedlove and Arnold, 1981), whereas estrogenic metabolites of testosterone appear to control cell survival in the two forebrain regions (Arai et al, 1996;Simerly et al, 1997). Moreover, gonadal steroid hormones increase cell death in the anteroventral periventricular nucleus while decreasing death in the bed nucleus of the stria terminalis and SNB.…”

Section: Discussionmentioning

confidence: 99%

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

Jacob

Bengston²,

Forger³

2005

Journal of Neuroscience

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Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target muscles in the perineum, bulbocavernosus (BC), and levator ani (LA) normally degenerate in female rodents. Death of the motoneurons and muscles can be prevented by androgen treatments around the time of birth. To identify the intracellular mechanisms underlying hormone-dependent survival of this neuromuscular system, we examined mice with a targeted disruption of the pro-death gene Bax. SNB motoneuron number was increased in female Bax؊/؊ mice, whether measured using immunolabeling for a motoneuron-specific marker or retrograde labeling with the fluorescent tracer Fluoro-Gold. Based on retrograde tracing, the sex difference in SNB cell number is eliminated in Bax؊/؊ mice. Thus, Bax is required for sexually dimorphic motoneuron death in the SNB, and motoneurons rescued by Bax deletion project their axons to the periphery. Mean soma size in the SNB of Bax؊/؊ females is reduced, however, and there is a subpopulation of very small cells in the SNB of female knock-outs. In addition, the BC muscle was not identified in any female, regardless of Bax gene status. All females possessed a small LA muscle, and Bax deletion resulted in a tripling of LA fiber number in females. This increase was small, however, relative to the Ͼ50-fold sex difference in LA muscle fiber number. Thus, the sex difference in the perineal muscles is mostly unaffected by the absence of Bax protein, and SNB motoneuron number is dissociated from target muscle size in Bax؊/؊ animals.

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Section: Discussionmentioning

confidence: 99%

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

Jacob

Bengston²,

Forger³

2005

Journal of Neuroscience

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“…One possibility is that different hormonal metabolites modulate cell death in the AVPV and BNSTp. Estradiol mimics effects of testosterone on cell death in AVPV (44), but the testosterone metabolites that regulate apoptosis in the BNSTp have not been examined. Steroid hormone receptors may also be expressed differentially in the two nuclei.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Bax eliminates sex differences in the mouse forebrain

Forger

Rosen²,

Waters³

et al. 2004

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

202

215

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Several of the best-studied sex differences in the mammalian brain are ascribed to the hormonal control of cell death. This conclusion is based primarily on correlations between pyknotic cell counts in development and counts of mature neurons in adulthood; the molecular mechanisms of hormone-regulated, sexually dimorphic cell death are unknown. We asked whether Bax, a member of the Bcl-2 family of proteins that is required for cell death in many developing neurons, might be essential for sex differences in neuron number. We compared Bax knockout mice and their WT siblings, focusing on two regions of the mouse forebrain that show opposite patterns of sexual differentiation: the principal nucleus of the bed nucleus of the stria terminalis, in which males have more neurons than do females, and the anteroventral periventricular nucleus (AVPV), where females have more neurons overall and many more dopaminergic neurons than do males. Testosterone, or its metabolites, is responsible for the sex differences in both nuclei. A null mutation of the Bax gene completely eliminated sex differences in overall cell number in both the principal nucleus of the bed nucleus of the stria terminalis and AVPV. Thus, Bax-dependent cell death is required for sexual differentiation of cell number, regardless of whether testosterone decreases or increases cell death. In contrast, the sex difference in AVPV dopaminergic cell number, as measured by tyrosine hydroxylase immunohistochemistry, was not affected by Bax gene deletion, demonstrating heterogeneity of mechanisms controlling cell number within a single nucleus.

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“…If this dose is reduced, the rat goes through puberty and carries out a small number of ovulations, the number being inversely related to the dose of steroid given (Arai & Matsumoto 1978, Arai et al 1996. Clearly, the effect of the partial steroid doses leaves part of the ovulatory mechanism of the brain intact.…”

Section: What Are Ovulons?mentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Geoffrey Harris and my brush with his unit

Raisman

2015

Journal of Endocrinology

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Geoffrey Harris is chiefly known for his demonstration of the control of the pituitary gland by the portal vessels coming from the hypothalamus. This does not do justice to his extraordinary contribution to biology. Harris' life's work was central in demonstrating the brain/body interactions by which animals and humans adapt to their environment, and above all the control of that most crucial and proximate of all evolutionary eventsreproduction. In this brief review, I have tried to put Geoffrey Harris' work in the context of the scientific thinking at the time when he began his work, and above all, the contribution of his mentor, FHA Marshall, on whose towering shoulders Harris rose. But this is mainly my personal story, in which I have tried to show the debt that my work owed to Harris and especially to my dear friend, the late Keith Brown-Grant in Harris' team. I myself was never an endocrinologist, but over a short period in the early 1970s, under the influence of such inspirational mentors, and using purely anatomical methods, I was able to demonstrate sexual dimorphism and hormone-dependent sexual differentiation in the connections of the preoptic area, regeneration of the median eminence, the ultrastructure of apoptosis, the requirement for the suprachiasmatic nuclei in reproductive rhythms, the existence of non-rod or cone photoreceptors in the albino rat retina and, later, the expression of vasopressin by solitary (one in 600) magnocellular neurons in the polydipsic di/di Brattleboro mutant rat; this phenomenon was subsequently shown to be due to aC1 reading frameshift. I end this brief overview by mentioning some of the abiding and fascinating mysteries of the endocrine memory of the brain that arise from Harris' work on the control of the endocrines, and by pointing out how the current interest in chronobiology emphasises what a Cinderella the endocrine mechanisms have become in current brain imaging studies.

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Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats

Cited by 154 publications

References 22 publications

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

Deletion of Bax eliminates sex differences in the mouse forebrain

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Geoffrey Harris and my brush with his unit

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