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N J Maclusky

Publications and source records attributed to N J Maclusky.

11 recordsLinked to original sources

Synaptic remodeling induced by gonadal hormones: neuronal plasticity as a mediator of neuroendocrine and behavioral responses to steroids.

During recent decades, it has become a generally accepted view that structural neuroplasticity is remarkably involved in the functional adaptation of the CNS. Thus, cellular morphology in the brain is in continuous transition throughout the life span, as a response to environmental stimuli. The effects of the environment on neuroplasticity are mediated by, to some extent, the changing levels of circulating gonadal steroid hormones. Today, it is clear that the function of gonadal steroids in the brain extends beyond simply regulating reproductive and/or neuroendocrine events. In addition, or even more importantly, gonadal steroids participate in the shaping of the developing brain, while their actions during adult life are implicated in higher brain functions such as cognition, mood and memory. A large body of evidence indicates that gonadal steroid-induced functional changes are accompanied by alterations in neuron and synapse numbers, as well as in dendritic and synaptic morphology. These structural modifications are believed to serve as a morphological basis for changes in behavior and cellular activity. Due to their growing functional and clinical significance, the specificity, timeframe, as well as the molecular and cellular mechanisms of hormone-induced neuroplasticity have become the focus of many studies. In this review, we briefly summarize current knowledge and the most significant recent discoveries from our laboratories on estrogen- and dehydroepiandrosterone-induced synaptic remodeling in the hypothalamus and hippocampus, two important brain areas heavily involved in autonomic and cognitive operations, respectively.

Animals↗

Sex differences in estrogen receptor binding in the rat hypothalamus: effects of subsaturating pulses of estradiol.

The effects of subsaturating pulses of estradiol on cell nuclear retention of estrogen receptors in brain regions of male and female rats were determined. In the first experiment, age-matched adrenalectomized/gonadectomized (ADX/GDX) rats were killed 1 h after i.v. injection of a subsaturating dose of free estradiol (1.0 microgram/kg b. wt.) and cell nuclear estrogen receptor binding was measured in microdissected brain areas by an in vitro exchange assay. As we have previously reported with saturating doses of estradiol (3.6-36.0 micrograms/kg b. wt.), a greater concentration of receptors was measured in the ventromedial nucleus (VMN), periventricular preoptic area (PVPOA), and medial preoptic area (mPOA) of the female than in the same regions of the male brain. Binding levels did not differ between the sexes in the bed nucleus of the stria terminalis, arcuate nucleus, or the corticomedial amygdala. In the second experiment, GDX/ADX male and female rats received either a single or double pulse of 0.5 microgram estradiol/kg b. wt. administered 6 h apart. Rats were killed 1 h after the second pulse. In animals treated with a single pulse of estradiol 1 h before sacrifice, higher concentrations of estrogen binding were measured in the female VMN and PVPOA than in the male. Except in the mPOA, the concentration of estrogen receptor binding measured was not different from that measured in animals that had received an additional, earlier pulse of estradiol. In this area, receptor concentrations were lower in male rats treated with two pulses than in males treated with one pulse.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Estrogen effects on the synaptology and neural membranes of the rat hypothalamic arcuate nucleus.

The concept of estrogen-induced "sexual differentiation of the brain" has been a useful focus for investigation. However, it has become clear that the action of estrogen on the rat brain is lifelong, including effects on neurogenesis in the fetus, synaptogenesis in the newborn, and synaptic remodeling in the adult. Estrogen imparts sex differences in the rat's brain by shaping synaptology, postsynaptic membranes, and glia within the arcuate nucleus. These effects of estrogen on the arcuate nucleus also could underlie sexual maturation in both sexes and the development of senescent constant estrus in females.

Animals↗

A study of cytoplasmic and nuclear estrogen and progestin receptors in gynecologic neoplasms.

A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P) receptors and their in vitro determination is described. The method was applied to several uterine or ovarian surgical specimens to evaluate their steroid hormone "dependence". The results suggest that low cytoplasmic E receptor levels (ERc) are associated with higher nuclear E receptor (ERn) levels but no apparent correlation was observed between PRc and ERn levels. The method appeared to be suitable for screening steroid hormone receptor content in tumor tissues and may provide better estimation of steroid dependence since both cytoplasmic and nuclear compartments can be studied simultaneously.

Adult↗

The specificity of oestrogen receptor in brain, pituitary and uterus.

1 The specificity of oestrogen receptor in rat brain regions (hypothalamus, amygdala and cortex), pituitary and uterus was studied by measurement of the inhibition of 17beta-oestradiol high affinity binding in cytosol, in the presence of unlabelled putative inhibitors of binding. 2 Binding was inhibited only by those of the compounds tested that possessed oestrogen agonist or antagonist activity. The affinities were estimated and the ranking order of the compounds was the same in all tissue sources of cytosol and corresponded to the ranking order of agonist or antagonist potency. 3 There were some significant differences between some of the estimated affinities in different tissues, these being seen most commonly between pituitary and hypothalamus on one hand and uterus on the other. 4 The possibility of heterogeneity of oestrogen receptor is discussed.

Amygdala↗

5alpha-Dihydrotestosterone (DHT) receptors in rat brain and pituitary cell nuclei.

Gonadectomized-adrenalectomized (GX-ADX) adult male rats were injected iv with 2-4 mug/kg [1,2-3H]DHT and sacrificed 2 h later. Whole tissue homogenates and purified cell nuclear fractions were prepared from various brain regions and the pituitary and analyzed for radioactivity. Cell nuclei from pituitary and most limbic-hypothalamic regions (but not cerebral cortex) concentrated radioactivity (per unit protein) over whole tissue levels. The highest levels of nuclear-associated radioactivity were present in pituitary, hypothalamic and septal tissues. Analysis of radioactivity by double isotope dilution, chromatography, and recrystallization revealed that unmetabolized DHT represented 96 and 95% of the nuclear-associated radioactivity in pituitary and pooled limbic-hypothalamic structures, respectively. Simultaneously administered 100-fold molar excesses of unlabeled 5betaDHT, progesterone or corticosterone did not reduce nuclear-retained [3H]DHT, while unlabeled 5alphaDHT competed strongly. The anti-androgen, cyproterone acetate, competed at doses capable of of blocking androgen-mediated neuroendocrine effects. Levels of nuclear-retained [3H]DHT were negligible in intact males, but rose markedly 24 h after castration-adrenalectomy, remaining stable for 2 weeks post-operatively. Density gradient centrifugation of pituitary or brain cell nuclear salt extracts (0.4M KCl) revealed the [3H]DHT bound to a macromolecule sedimenting at 3--4S. The characteristics of DHT brain and pituitary cell nuclear binding are compared with the respective characteristics of neural cytosol and ventral prostate nuclear androgen binding components. These preliminary data suggest the existence of the functional, steroid-specific, stereospecific cell nuclear androgen receptor in the adult rat brain and pituitary.

Adrenalectomy↗