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F Naftolin

Publications and source records attributed to F Naftolin.

At least 145 records · Page 8Linked to original sources
PubMed1991

Loss of sexual dimorphism in rat arcuate nucleus neuronal membranes with reproductive aging.

Arcuate neurons of the rat hypothalamus have a sexual dimorphic membrane phenotype: quantitative analysis of freeze-fracture replicas has revealed that a population of intramembrane protein particles (IMP) of small size (less than 10 nm) is enriched in the plasma membrane of perikarya and dendritic shafts of cycling females compared to males, whereas a population of large IMPs (greater than 10 nm) is enriched in the membrane of dendritic shafts of males. This different membrane organization is associated with a sex dimorphic synaptic connectivity. To determine whether sex differences in neuronal membrane are affected by reproductive senescence, IMPs were assessed in freeze-fracture replicas of arcuate neuronal plasma membranes of male and female Sprague-Dawley rats aged 3, 15, and 18 months. Three-month-old cycling females were studied on the morning of estrus. Senescent females were in constant estrus (15 months old) or in constant diestrus (18 months old). Young females had more IMPs with diameters under 10 nm in the inner and outer leaflets of the plasma membrane of the perikarya and dendritic shafts compared to males of the same age. In addition, young males showed an increased number of large (greater than 10 nm) IMPs in the outer membrane leaflet of dendritic shafts. No sex differences were detected in the membrane of dendritic spines. In senescent females the number of small IMPs was decreased in the perikarya and dendritic shafts compared to young females while the number of large particles was increased in the outer leaflet of the membrane of dendritic shafts, reaching values similar to those observed in males. IMP counts were not modified with aging in males and in dendritic spines of females. These results indicate that reproductive aging in female rats is associated with a remodeling of neuronal plasma membranes in arcuate neurons.

Aging↗
PubMed1991

Convergent vasopressinergic and hippocampal input onto somatospiny neurons of the rat lateral septal area.

Electron microscopic immunocytochemistry, was combined with acute anterograde axon degeneration, following transection of the fimbria-fornix, to describe the innervation of somatospiny neurons by vasopressin-immunoreactive and degenerated hippocamposeptal axon terminals in the rat lateral septal area. Vasopressin-immunopositive boutons characterized by symmetric synaptic membrane specializations, and the degenerated hippocamposeptal axon terminals which form asymmetric synaptic contacts, frequently terminate on the same dendritic and somatic profiles, and particularly on the somata of somatospiny neurons. Although hippocamposeptal fibers predominantly form axospinous synapses in the lateral septal area, they terminate mainly on the dendritic shafts and soma of the vasopressin-receptive neurons. Of 720 vasopressin-immunoreactive terminals in the mediolateral part of the lateral septal area, 80% form synaptic contacts with dendritic shafts; 50% on small (distal) dendritic profiles and 30% on large (proximal) dendrites. Synaptic contacts between vasopressin-immunoreactive terminals and dendritic spines were not observed. The remaining 20% of immunoreactive boutons formed axosomatic synaptic contacts with a total of 58 neurons; 31% of these neurons exhibited somatic spines in the plane of the section analysed. Previous studies have demonstrated that in the lateral septal area vasopressin modulates the action of the excitatory amino acid-containing hypocamposeptal fibers, and also plays a role in the maintenance of long term potentiation evoked by fimbria-fornix stimulation. The convergent vasopressinergic and hippocampal input onto the same somatospiny neurons of the lateral septal area suggests that these neurons are targets of these physiological actions.

Animals↗
PubMed1991

Estrogen induces ultrastructural changes in progesterone receptor-containing GABA neurons of the primate hypothalamus.

Estrogen affects gonadotrophin levels and sex behavior in monkeys. This action could be via inhibitory GABA-ergic neurons in the hypothalamus. We tested for direct estrogen actions on such neurons. Seven days after ovariectomy (OVX) or OVX + estrogen treatment (10 mg estradiol valerate in 1 ml sesame oil s.c. on the day of OVX), light- and electron-microscopic double immunostaining procedures were used for simultaneous visualization of immunoreactivity for progesterone receptors (PR) and glutamic acid decarboxylase (GAD), and to detect ultrastructural changes in PR-containing neurons in the arcuate and ventromedial hypothalamic nuclei of colchicine- and noncolchicine-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for PR was found only in cell nuclei, and estrogen treatment enhanced the intensity of the immunostaining: in estrogen-treated monkeys in the arcuate nucleus 62%, while in the ventromedial nucleus 42% of the neurons contained PR-immunoreactive nuclei. All of the PR-containing neurons were immunopositive for GAD in colchicine-pretreated monkeys. OVX induced whorl body formation, while estrogen treatment of OVX animals resulted in a large number of nematosomes. While all of the whorl bodies and the majority of nematosomes were observed in PR-immunopositive GAD neurons, nematosomes were also found in non-PR-containing GAD-immunoreactive cells.

Animals↗
PubMed1991

Astrocytes within the hypothalamic arcuate nucleus contain estrogen-sensitive peroxidase, bind fluorescein-conjugated estradiol, and may mediate synaptic plasticity in the rat.

Estrogen treatment induces synaptic plasticity accompanied by damaged structures and aggregates of peroxidase in astrocytes in the hypothalamic arcuate nucleus of the rat. Synaptic plasticity also occurs within the arcuate nucleus after physiologic surges of estrogen. Although the function of estrogen-induced peroxidase is unclear at present, in other systems peroxidase can generate free radicals by catalyzing the oxidation of some molecules, including estrogen. Because free radicals underlie remodeling in a number of tissues, estrogen-induced free radicals could mediate synaptic remodeling within the arcuate nucleus. Although they contain estrogen-inducible peroxidase, astrocytes do not contain estrogen receptors as measured by conventional techniques, suggesting that estrogen-inducible peroxidase arises from some novel mechanism. Estrogen could induce peroxidase within receptor-deficient astrocytes by binding to receptors in neurons and stimulating the release of some factor that interacts with astrocytes. Alternatively, estrogen could act directly on astrocytes in the absence of estrogen receptors. Although astrocytes in the hypothalamus of the rat do not contain classical nuclear estrogen receptors, they do bind fluorescein-conjugated estradiol in extranuclear sites. The distribution of fluorescein-conjugated estradiol binding within the hypothalamus overlaps that of peroxidase-rich astrocytes, and double labeling reveals many cells with the stellate morphology of astrocytes, containing both peroxidase and fluorescein-conjugated estradiol binding. However, because peroxidase and fluorescein-conjugated estradiol always occupy different compartments of the cell, the fluorescein-conjugated estradiol is not binding to peroxidase.

Animals↗
PubMed1990

Sexual differentiation of synaptic connectivity and neuronal plasma membrane in the arcuate nucleus of the rat hypothalamus.

Plasma membranes of the hypothalamic arcuate neurons of the rat show a sexually dimorphic phenotype: the numerical density of intramembrane protein particles is greater in females. Male and female Sprague-Dawley rats, 10, 20 and 100 days old, were studied in order to determine whether sexual differentiation of the neuronal plasma membrane in the soma of arcuate neurons is associated with the establishment of sex differences in the pattern of axo-somatic synaptic contacts. Axo-somatic synapses were counted in thin sections of the arcuate nucleus and intramembrane particles were assessed in freeze-fracture replicas of the neuronal membrane. The number of synapses per length of perikaryal membrane increased from day 10 to day 20 in both sexes, reaching by 20 days values similar to those found on day 100. A sex difference in the number of synapses was observed only in 20-day-old and 100-day-old rats: neurons from females showed a greater number of presynaptic inputs than males (P less than 0.05). This sex difference was abolished by administration of testosterone propionate to 5-day-old females. Quantitative evaluation of freeze-fracture replicas of the arcuate neuronal perikarya revealed sex differences in the numerical density of intramembrane particles at all time points studied: neurons from females contained significantly more particles in their plasma membranes than neurons from males or androgenized females of the same age (P less than 0.001). These results indicate that sexual differentiation of the plasma membrane in neuronal somas precedes the establishment of sex differences in axo-somatic synapses. The results are compatible with a possible role of neuronal membranes in the sexual differentiation of synaptic connectivity.

Animals↗
PubMed1990

Prazosin treatment does not affect progestin receptor induction in microdissected regions of the rat hypothalamus.

Sex differences in estrogen-induced progestin receptors have been described in specific regions of the rat brain. To determine if alpha 1-neurotransmission plays a role in the expression of the sex differences in progestin receptor induction, the effects of the alpha 1-antagonist, prazosin, on progestin binding in microdissected regions of the rat brain was determined. Adrenalectomized/gonadectomized male or female rats were administered various doses of estradiol benzoate (EB) in combination with prazosin. With all treatment paradigms, and in both sexes, no significant effect of prazosin treatment on progestin receptor levels was observed. These results are consistent with the idea that sex differences in the estrogen-induction of progestin receptors in the rat hypothalamus are not due to sex differences in the alpha 1-adrenergic regulation of progestin receptor synthesis.

Adrenergic Fibers↗
PubMed1990

Trophic effects of basic fibroblast growth factor on fetal rat hypothalamic cells: interactions with insulin-like growth factor I.

The existence of different growth factors within a single brain region suggests that developing brain cells are exposed to a variety of trophic factors throughout neurogenesis. Cooperative interactions between growth factors are known to orchestrate growth and differentiation of various cell types. We explored the possibility that two growth factors may interact in promoting in vitro growth in fetal hypothalamic cells. We found that basic fibroblast growth factor (b-FGF) exerts trophic effects on primary mixed hypothalamic cell cultures, on enriched hypothalamic neuronal cultures, and on hypothalamic glial cultures. In addition, b-FGF increased the growth rate of two virally transformed hypothalamic cell lines. Since insulin-like growth factor I (IGF-I) also promotes growth of rat hypothalamic cells in vitro, we examined the combined effects of b-FGF and IGF-I on hypothalamic cells. Significantly higher numbers of neurite-bearing cells were present in primary mixed hypothalamic cultures when b-FGF and IGF-I were added together than were added separately. The effect was additive. These results establish b-FGF as a putative hypothalamic neurotrophic factor and demonstrate potential coordinate interactions between IGF-I and b-FGF in stimulating the growth or survival of developing hypothalamic cells.

Animals↗
PubMed1990

Estrogen effects on the tuberoinfundibular dopaminergic system in the female rat brain.

Estrogen effects on tyrosine hydroxylase (TH), monoamine oxidase types A and B (MAO), and dopamine (DA) in microdissected regions of the hypothalamus, preoptic area and substantia nigra (SNR) of the female rat brain were investigated. Ovariectomized (OVX) young adult female rats were implanted with single silastic capsules containing 100% estradiol valerate (EV). Control rats received empty silastic capsules. Two weeks following capsule insertion, EV decreased TH activity and DA concentration in the arcuate nucleus (AN) while no significant changes in TH activity or DA concentration were observed in the SNR, ventromedial nucleus (VMN), suprachiasmatic nucleus, paraventricular nucleus, medial preoptic nucleus, or the periventricular preoptic nucleus. Although estrogen suppressed TH and DA in the AN, 2 weeks following removal of the estrogen containing capsules, TH activity and DA concentration were restored to control (OVX) levels. Suppression of MAO activity occurred in both the AN and the VMN of rats implanted with EV capsules and returned to OVX levels following the removal of the estradiol load. These results revealed that estrogen effects on TH and MAO activities and DA concentration in the midbrain are region specific and reversible; and that among the dopaminergic systems studied, estrogen effects on TH and DA are confined to the tuberoinfundibular dopaminergic system (TIDAS). Furthermore, these results support our hypothesis that estrogen is a key regulator of DA function in the TIDAS via effects on TH. The importance of these findings to the control of gonadotropin secretion and reproductive cyclicity is discussed.

Animals↗
PubMed1990

Gap junctions in the hypothalamic arcuate neurons of ovariectomized and estradiol-treated rats.

Freeze-fracture methodology was used to study the organization of the neuronal plasma membrane in the rat arcuate nucleus, an estrogen sensitive area of the hypothalamus. Freeze-fracture replicas were prepared from 6 adult ovariectomized rats injected with a single dose of 17 beta-estradiol and from 6 ovariectomized littermates injected with vehicle. Rats were sacrificed 2 days after the injection. Occasional gap junctions were observed in freeze-fractured neuronal membranes from both groups of animals and their incidence was increased (P less than 0.01) in estradiol treated rats. This study demonstrates gap junctions in arcuate neurons and suggests that these structures may be affected by gonadal hormones.

Animals↗
PubMed1990

Cryopreservation of human brain tissue.

Tissues from products of conception were examined to determine the feasibility of obtaining viable neural tissue after suction abortion at 9-12 weeks of gestation. The ventral mesencephalon, a prototype region whose maturation can be monitored and which is a potential tissue for transplantation, was identified in 32 of 120 cases. The tissue was then screened for the presence of infectious agents, while being held at -196 degrees C in cryopreservative solutions. Three of 32 specimens were found to be contaminated by normal vaginal bacteria; all other viral, fungal, and mycoplasma testing was negative. Thawed brain fragments retained high viability after storage in liquid nitrogen and when grown in vitro exhibited neuronal morphology, tyrosine hydroxylase immunoreactivity, and dopamine production. We have demonstrated that human fetal brain tissue can be cryopreserved in a manner which not only retains viability but allows normal phenotypic differentiation after thawing.

Brain↗
PubMed1990

Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture.

The hypothesis that insulin-like growth factor-I is a trophic factor for primary fetal rat hypothalamic cells was tested, since we previously reported a potent mitogenic effect of this peptide on virally-transformed hypothalamic cells. It was found that insulin-like growth factor-I produced significant and dose-dependent increases in the survival of fetal hypothalamic neurons in primary mixed glial/neuronal cultures. By 48 h in vitro, cultures treated with insulin-like growth factor-I (6 nM) had twice as many neurite-bearing cells as controls, while by day 15 a five-fold difference was present. The peptide was similarly active in promoting neuronal survival in neuron-enriched (98% neurons) hypothalamic cultures. Mixed hypothalamic cultures had specific binding sites for insulin-like growth factor-I. In addition, the neurons grown in the presence of insulin-like growth factor-I had a more differentiated morphology and had significantly higher levels of protein kinase C, an enzyme that increases during neurite formation and synaptogenesis. Finally, glial-enriched cultures (greater than 99% glial cells) obtained from the fetal hypothalamus showed increased [3H]thymidine incorporation in response to insulin-like growth factor-I. These results further support the contention that insulin-like growth factor-I is a neurotrophic factor and suggest that it may participate in the normal development of the hypothalamus by increasing neuronal survival/differentiation and stimulating glial growth.

Animals↗
PubMed1990

African green monkeys have sexually dimorphic and estrogen-sensitive hypothalamic neuronal membranes.

Previous studies have shown sex differences in intramembrane particle content in the arcuate neurons of the rat hypothalamus. In this study, freeze-fracture replicas were prepared from the infundibular hypothalamus of adult African green monkeys (Cercopithecus aethiops) in order to determine whether primates also have sexual dimorphism in neuronal membranes. Intramembrane particles (IMP) were quantitatively assessed in the perikaryal plasma membranes of infundibular neurons. Four groups of monkeys were studied: intact males, intact females, ovariectomized females injected with 20 mg of estradiol valerate over 10 days and ovariectomized females injected with vehicle (castor oil). Membranes from females showed an increased numerical density of IMPs when compared to males. Ovariectomy of females did not affect IMP content, while estrogen administration resulted in a significant decrease in IMP numerical density to reach male values. These findings indicate a sex difference in neuronal membranes in the hypothalamus of monkeys and suggest that as in rodents, neuronal plasma membrane organization in higher primates may be modulated by gonadal steroids.

Animals↗
PubMed1990

Estrogen induction of a small, putative K+ channel mRNA in rat uterus.

Estrogen causes dramatic long-term changes in the activity of the uterus. Here we report the molecular cloning of a small (700 base) uterine mRNA species capable of inducing a slow K+ current in Xenopus oocytes. The 130 amino acid protein encoded by this mRNA species has a predicted structure that does not resemble that of previously described voltage-dependent channels from mammalian sources. It is, however, similar to structural motifs found in certain prokaryotic ion channels. The induction of this mRNA by estrogen is rapid; this uterine mRNA species is not detectable in uteri from estrogen-deprived rats, but is substantially induced after 3 hr of estrogen treatment. These results support a critical role for regulation of ion channel expression by estrogen in the uterus.

Amino Acid Sequence↗
PubMed1990

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↗
PubMed1990

The effects of estradiol on the growth patterns of estrogen receptor-positive hypothalamic cell lines.

Although it appears that the perinatal development of sexual phenotype in the rodent brain is determined by exposure to estradiol, generated locally via aromatization of androgen, the mechanisms underlying this process are not fully understood. We have, therefore, developed an in vitro model of hormone action based upon examining the effects of sex steroids on SV-40-transformed fetal rat hypothalamic cell lines. Using serum-free growth factor-deficient conditions the effects of 17 alpha- and 17 beta-estradiol, testosterone, dihydrotestosterone (DHT), and tamoxifen on survival of two estrogen-binding rat hypothalamic cell lines were examined. In one cell line, RCF-8, both 17 beta-estradiol and testosterone increased survival at picomolar concentrations. This effect was blocked by tamoxifen, but could not be reproduced by the nonaromatizable androgen DHT or the inactive isomer 17 alpha-estradiol. In the other cell line, RCA-6, addition of 17 beta-estradiol led to inhibition of cellular proliferation, which was reversed by the addition of tamoxifen. In an estrogen receptor-negative hypothalamic cell line, RCF-12, estradiol had no net effect on the growth pattern. In summary, the estrogen-binding capacity and the responsiveness to physiological concentrations of estradiol and testosterone, but not DHT, make the RCF-8 cell line a potential in vitro model of hypothalamic sexual differentiation. The use of estrogen-sensitive hypothalamic cell lines provides a unique opportunity for studying the cellular mechanisms underlying this process.

Animals↗