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F Naftolin

Publications and source records attributed to F Naftolin.

At least 91 records · Page 5Linked to original sources
PubMed1995

Morphological evidence for a galanin-opiate interaction in the rat mediobasal hypothalamus.

It is well established that hypothalamic galanin- and beta-endorphin-containing circuits play important roles in the neuroendocrine regulation of pituitary hormone secretion and sexual behaviors, as well as in feeding. Recent experimental evidence suggests that an opiate-galanin interaction may be involved in these neuroendocrine responses. In particular, galanin and beta-endorphin have been shown to stimulate prolactin release from the pituitary, and concurrently, evoke feeding in the rat. The present study was designed to elucidate the morphological component underlying these responses in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine-pretreated female rats were double immunostained for galanin and beta-endorphin. A dark blue nickel ammonium sulfate-intensified diaminobenzidine reaction was used to visualize galanin profiles, while beta-endorphin neurons were labeled with a light brown diaminobenzidine reaction. Light microscopy revealed putative connections between galanin boutons and beta-endorphin cells. Electron microscopic examination showed that galanin boutons form axo-somatic and axo-dendritic synaptic connections with beta-endorphin neurons. The vast majority (89.6%) of the beta-endorphin-immunoreactive neurons were found to be contacted by galanin-immunopositive fibers in the hypothalamus. To determine the origin of the galanin fibers innervating this region, the arcuate nuclei of additional rats were isolated unilaterally using a Halász-knife. After a ten day survival period, immunostaining was carried out for galanin. The relative surface occupied by galanin immunoreactive profiles on the ipsi- and contralateral sides were compared using an image analyzer. This analysis revealed that deafferentation of the arcuate nucleus did not decrease the density of galanin immunoreactive profiles on the isolated side of the arcuate nucleus compared to the control side, thus, indicating that the galanin boutons contacting beta-endorphin cells are most probably of local origin. These studies support the proposal that galanin-evoked prolactin secretion and feeding behavior may, in part, be mediated by enhanced beta-endorphin release and raises the possibility that a hypothalamic galanin-beta-endorphin axis may operate in the control of other pituitary hormones.

Animals↗
PubMed1995

Distribution of estrogen receptor-immunoreactive cells in monkey hypothalamus: relationship to neurones containing luteinizing hormone-releasing hormone and tyrosine hydroxylase.

The precise sites and mechanisms by which gonadal steroids influence the activity of neuroendocrine cells controlling pituitary hormone secretion are poorly understood. The present study has determined the distribution of estrogen receptor (ER)-immunoreactive cells in the monkey hypothalamus and examined whether ERs are expressed by luteinising hormone-releasing hormone (LHRH)-and/or dopamine-containing neurones. The distribution of ER-immunoreactive cells was determined in ovariectomised (n = 2) and estrogen plus progesterone-treated (n = 2) cynomolgus macaques and in a single ovariectomised African green monkey. Large numbers of cells immunoreactive for the ER were detected in the preoptic area, bed nucleus of the stria terminalis, periventricular area and ventromedial and arcuate nuclei of all monkeys irrespective of the steroid status. Smaller numbers of ER-immunoreactive cells were found in the paraventricular, but not supraoptic nucleus. Double-labeling experiments in sections from all 5 monkeys revealed that none of the 432 LHRH neurons examined possessed detectable ER immunoreactivity. Neurones stained for tyrosine hydroxylase (TH) were identified in the A11, A12, and A14 cell groups and, although A11 and A12 neurones were intermingled amongst and found adjacent to ER-immunoreactive cells, none of the 1,652 TH-immunoreactive cells examined contained ER immunoreactivity. These results show that ER-immunoreactive cells in the monkey hypothalamus are distributed in a manner similar to that observed in other mammalian species although not all brain regions reported to contain progesterone receptors (PRs) in these species of monkey were found to express ERs. The double-labelling experiments provide further evidence that LHRH neurones do not possess ERs and indicate that, as in other species, estrogen influences on primate LHRH neurones are indirect and/or non-genomic in nature. Unlike the rat and sheep, no evidence was found for ER immunoreactivity in hypothalamic dopaminergic neurones of the monkey. The discrepancy in ER and reported PR receptor localisation within specific hypothalamic nuclei as well as in dopaminergic neurones raises the possibility that not all PR-containing cells may express ERs in the primate hypothalamus.

Animals↗
PubMed1995

Phytoestrogen influences on the development of behavior and gonadotropin function.

The effect of phytoestrogens on the sexual differentiation of gonadotropin function was examined by neonatal exposure of pups through milk of rat dams fed a coumestrol (100 micrograms/g), control, or chow diet during the "critical period" of the first 10 postnatal days or throughout the 21 days of lactation. In females, exposure to coumestrol throughout the period of lactation produced growth suppression and an acyclic condition in early adulthood resembling the premature anovulatory syndrome. When the period of treatment was restricted to the first 10 postnatal days, however, no effects on vaginal cyclicity were seen. The 10-day exposure period produced more marked effects in males, resulting in transitory reductions in body weight in weanling males and reductions in mount and ejaculation frequency and a prolongation of the latencies to mount and ejaculate. Testicular weights and plasma testosterone levels did not differ among treatment groups, suggesting that the deficits in male sexual behavior were not due to deficits in adult gonadal function. Few effects of chow treatment were observed. However, significant differences from controls were apparent for weight at vaginal opening in females, and mount rate for chow-treated males was intermediate between that of controls and that of the coumestrol-treated group. These data provide evidence that lactational exposure to phytoestrogen diets can alter neuroendocrine development in both female and male rats.

Animal Feed↗
PubMed1995

The ovarian renin-angiotensin system. A paracrine-intracrine regulator of ovarian function.

We present a review that considers the regulation of ovarian function by the ovarian renin-angiotensin system. Evidence is presented that shows the ovarian renin-angiotensin system can regulate normal ovarian function by paracrine and intracrine mechanisms. In addition, the complexity that is inherent in the renin-angiotensin system conferred by multiple biological angiotensin peptides and multiple receptors is discussed. Evidence that a dysfunctional OVRAS induces ovarian pathology such as polycystic ovarian disease is also presented.

Animals↗
PubMed1994

Aromatase- (estrogen synthetase) immunoreactive neurons in the rat septal area. A light and electron microscopic study.

The aromatase enzyme (estrogen synthetase) catalyzes the conversion of testosterone to estrogen in peripheral and central nervous tissue. Light and electron microscopic immunocytochemistry was used to study the localization of this enzyme in the septal area of adult male and female albino rats. Aromatase-immunoreactivity was found restricted to neuronal somata and dendritic arbors, and no sex differences were detected in its distribution or intensity. Most aromatase-immunoreactive neurons formed two oblique bands in the lateral and the medial zones of the lateral septum; in addition, labeled cells were present in the septohippocampal nucleus and the laterodorsal portion of the bed nucleus of the stria terminalis. Electron microscopy revealed that the majority of aromatase-positive neurons in the lateral septum exhibit somatic spines, a characteristic marker of a neuron population that is known to contribute to local and extraseptal projections. The presence of aromatase in lateral septal somatospiny neurons suggests that estrogen formed by these neurons may be critically involved in the septal control of steroid-dependent behaviors.

Animals↗
PubMed1994

Regulation of arcuate nucleus synaptology by estrogen.

Estrogen modulates the synaptology of the hypothalamic arcuate nucleus during sexual differentiation of the rat brain in both males and females. In males, testosterone of gonadal origin is converted to estrogen in the brain by an enzyme, aromatase, which is also present in females. The exposure of the male's hypothalamus to relatively high levels of estrogen (following a perinatal testosterone surge) leads to the development of a pattern of synaptogenesis which does not support an estrogen-induced gonadotrophin surge in the adult. In female rats, hypothalamic development occurs with permissively low levels of estrogen, enabling a midcycle estrogen-induced gonadotrophin surge and ovulation in adulthood. During adult reproductive life in female rats, circulating estrogen modulates the synaptology of the arcuate nucleus. The most physiological example of this is the 30-50% loss of axosomatic synapses following the preovulatory estrogen surge on diestrus-proestrus. Studies on post-synaptic membranes of the arcuate nucleus reveal sex differences in membrane organization and protein content which are estrogen-dependent. Estrogen apparently stimulates endocytosis of areas of post-synaptic membrane that are dense with small intramembranous protein particles, resulting in a reduction in the number of small intramembranous particles. This also appears to be the physiologic mechanism of neuronal changes in females during the estrus cycle. Repeated exposure to preovulatory levels of estrogen may lead to an age-related decline in reproductive capacity in female rats. Aging females lose the estrogen-induced gonadotrophin surge responsible for ovulation. This loss of function may result from a cumulative estrogen effect during the repeated ovarian cycles which results in a reorganization of the synaptology on which regulates the estrogen-induced gonadotrophin surge. The membrane organization of the senescent constant estrus aged female appears indistinguishable from the males. The hypothalamic circuits modulated by estrogen have yet to be delineated. However, recent research has shown that GABA, the monoamines, and several neuropeptides are participants in the estrogen-sensitive network which regulates GNRH secretion. In this regard, present work shows estrogen-induced changes in GABA and dopamine synapses in the arcuate nucleus.

Aging↗
PubMed1994

Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus.

The influence of gonadal steroids on the ultrastructure of glial cells and on the immunoreactivity for the specific astrocytic marker glial fibrillary acidic protein (GFAP) has been assessed in the neuroendocrine hypothalamus. The following parameters were analyzed in the arcuate nucleus of adult female rats: the number and the surface density of cells immunoreactive for GFAP, the number of glial profiles showing bundles of glial filaments, the size of the bundles of glial filaments, and the proportion of neuronal perikaryal membrane apposed by glial processes. These parameters were studied during the different phases of the estrous cycle, after ovariectomy, and after the administration of estradiol or progesterone to ovariectomized rats. No significant differences were detected in the number of GFAP-immunoreactive cells among the different experimental groups. The surface density of GFAP-immunoreactive material, the number of glial profiles in the neuropil, and the proportion of neuronal perikaryal membrane covered by glia were increased in the afternoon of proestrus and in the morning of estrus compared with other phases of the estrous cycle or to ovariectomized rats and showed a rapid (5 h) and reversible increase in ovariectomized rats injected with 17 beta estradiol, with a maximal effect by 24 h after the administration of the hormone. In contrast, the size of the bundles of glial filaments was decreased in the afternoon of proestrus, in the morning of estrus, and by the administration of estradiol to ovariectomized rats. The parameters studied were not affected by the administration of progesterone. However, progesterone (300 micrograms/rat) blocked the effects of 17 beta estradiol (1, 10, and 300 micrograms). The results suggest that glial cells may be actively involved in the modulation of neuroendocrine events by the hypothalamus.

Animals↗
PubMed1994

Pubertal development of estrogen receptors in the rat brain.

The regional distribution of estrogen receptors (ER) was studied in the brain of the female rat over the peripubertal period. Increases were observed in nuclear ER occupation as well as cytosolic progestin receptor induction in the period leading up to the time of vaginal opening, consistent with an increased availability of estrogen to the brain. ER binding capacity, however, was remarkably similar in pre- and postpubertal rats. Using a microdissection-based nuclear ER assay, small increases in the total ER content of the hypothalamic ventromedial and arcuate nuclei were observed in the female at around the time of the onset of reproductive cyclicity. In vivo autoradiographic studies confirmed the existence of a small increase in estrogen binding in these two brain regions at around the time of vaginal opening, as well as transient increases in estrogen retention within the preoptic area and bed nucleus of the stria terminalis. These changes in estrogen binding in the brain may play a role in pubertal alterations in the feedback sensitivity of the brain to circulating estrogen.

Aging↗
PubMed1994

Influence of phytoestrogen diets on estradiol action in the rat uterus.

The influence of coumestrol on the action of estradiol was examined in oral and parenteral tests. Coumestrol did not antagonize the uterotrophic action of estradiol when administered either prior to, or jointly with, E2 treatment, or when administered orally or parenterally. Additive effects on estradiol stimulation of uterine weight and reduction of cytosolic estrogen receptor binding were observed following oral, but not parenteral, administration of coumestrol. On the other hand, coumestrol pretreatment did appear to dampen estradiol's induction of progestin receptors, uterine protein, and nuclear estrogen receptor binding. However, even at those endpoints where coumestrol pretreatment did dampen estradiol action, coumestrol itself produced an estrogenic response. These findings contradict the assumption that all phytoestrogens are necessarily antiproliferative agents and argue for specific identification of the actions of each chemical.

Administration, Oral↗
PubMed1994

Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms.

It is now obvious that the CNS is capable of undergoing a variety of plastic changes at all stages of development. Although the magnitude and distribution of these changes may be more dramatic in the immature animal, the adult brain retains a remarkable capacity for undergoing morphological and functional modifications. Throughout development, as well as in the postpubertal animal, gonadal steroids exert an important influence over the architecture of specific sex steroid-responsive areas, resulting in sexual dimorphisms at both morphological and physiological levels. We are only now beginning to gain insight into the mechanisms involved in gonadal steroid-induced synaptic changes. The number of synaptic inputs to specific neuronal populations is sexually dimorphic and this can be modulated by changes in the sex steroid environment. These modifications can be correlated with other morphological changes, such as glial cell activation, that are occurring simultaneously in the same anatomical area. Indeed, the close physical relationship between glial cells and neuronal synaptic contacts makes them an ideal candidate for participating in this process. Interestingly, not only can the morphology and immunoreactivity of glial cells be modulated by gonadal steroids, but a close negative correlation between the number of synapses and the amount of glial ensheathing of a neuron has been demonstrated, suggesting an active participation of these cells in this process. Glia have sex steroid receptors, are capable of producing and metabolizing steroids, and can produce other neuronal trophic factors in response to sex steroids. Hence, their role in gonadal steroid-induced synaptic plasticity is becoming more apparent. In addition, there is recent evidence that this process may involve certain cell surface molecules, such as the N-CAMs, since a specific isoform of this molecule, previously referred to as the embryonic form, is found in those areas of the brain which maintain the capacity to undergo synaptic remodelling. However, there is much work to be done in order to fully understand this phenomenon and before bringing it into a clinical setting in hopes of treating neurodegenerative diseases or injuries to the nervous system.

Androgens↗
PubMed1994

Gonadal steroids as promoters of neuro-glial plasticity.

Estradiol induces coordinated modifications in the extension of glial and neuronal processes in the arcuate nucleus of the hypothalamus of adult female rats. This hormonal effect results in natural fluctuations in the ensheathing of arcuate neurons by glial processes and these glial changes are linked to a remodelling of inhibitory GABAergic synapses during the estrous cycle. Hormonally induced glial and synaptic changes appear to be dependent on specific recognition or adhesion molecules on the neuronal and/or glial membranes.

Animals↗
PubMed1994

Gonadal hormone regulation of insulin-like growth factor-I-like immunoreactivity in hypothalamic astroglia of developing and adult rats.

The influence of gonadal steroids on insulin-like growth factor I (IGF-I)-like immunoreactivity was assessed in the rat arcuate nucleus, an area of the hypothalamus that regulates pituitary secretion. IGF-I-like immunoreactivity was observed in hypothalamic cells with the morphological aspects of tanycytes and astrocytes. The surface density of IGF-I-like immunoreactive glia increased with puberty in the arcuate nucleus of male and female rats, while decreasing with age in other brain areas. Gender differences in the surface density of IGF-I-like immunoreactive glia were detected in adult animals, with males and androgenized females having significantly higher values than normal females. In the latter, the surface density of IGF-I-like immunoreactive glia was increased in the afternoon of proestrus and in the morning of estrus compared to the morning of proestrus, diestrus and metestrus. In addition, IGF-I-like immunoreactivity showed a dose-dependent increase in ovariectomized rats injected with 17 beta-estradiol, but not in those receiving 17 alpha-estradiol. The effect of 17 beta-estradiol was blocked by simultaneous administration of progesterone, while this hormone alone had no effect. These results indicate that IGF-I-like immunoreactivity in arcuate glial cells is affected by the hormonal environment and suggest that IGF-I-like immunoreactive glia may be involved in neuroendocrine events within the hypothalamus.

Animals↗
PubMed1994

Differential regulation of astrocyte plasminogen activators by insulin-like growth factor-I and epidermal growth factor.

Rat astrocytes synthesize and secrete two types of plasminogen activators (PAs), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), whose functions are related to cell proliferation, migration, and differentiation during development. The regulation of PAs produced by brain astrocytes is poorly understood. In a previous report we demonstrated that t-PA and u-PA are each independently regulated by cAMP-dependent protein kinase and protein kinase-C. In the present study we examined the effects of three well characterized astrocyte mitogens, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF), on the PA activities produced and secreted by rat astrocytes in vitro. We found that IGF-I and EGF increase cell-associated total PA activity in astrocyte-conditioned medium (CM). The effects of both growth factors were dose and time dependent, and maximal stimulation was achieved after 72 h of treatment with the highest dose tested (100 nM). IGF-I stimulated the cell-associated PA activity more than the CM activity, whereas EGF showed an opposite pattern, suggesting that the secretion of PA is differentially modulated by IGF-I and EGF. PDGF had no effect on astrocyte PA activities at any dose or time point included in the study. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/zymography showed type-specific changes in CM and cell-associated PA activity after growth factor treatment. IGF-I stimulated only t-PA, whereas EGF induced a marked increase in u-PA activity and a more limited increase in t-PA. PDGF did not modify either t-PA or u-PA activity. In summary, our results show that IGF-I and EGF each had different effects on PA activities, whereas PDGF had no effect. This diversity in the patterns of growth factor regulation of PAs suggests that the production of astrocyte PAs is not simply related to mitogenesis. More likely, astrocyte PAs are involved in a wide range of growth factor-mediated actions in the developing brain.

Animals↗
PubMed1994

Stromal spindle cells contain aromatase in human breast tumors.

In situ synthesis of estrogens by breast cancer tissue provides a potential explanation for the high concentrations of estradiol in mammary neoplasms in postmenopausal women. A major metabolic pathway for estrogen biosynthesis is the conversion of androstenedione to estrone via the enzyme aromatase. Biochemical studies have demonstrated aromatase in tumor tissue, but at relatively low and not clearly biologically significant levels. The present study tested the hypothesis that tumor levels of aromatase, albeit low, could be biologically important if present in high concentrations in focal clusters of specific cell types. A pilot study used an immunohistochemical method in frozen sections of fresh breast tumors as an optimal means to detect aromatase. Twelve of 18 tumors contained aromatase-positive cells, some with highly intense staining. A follow-up study then attempted to precisely define the types of cells containing aromatase and correlate the immunohistochemical findings with biochemical aromatase activity. A modified H-score (histological scoring system) was used to semiquantitate the amount of aromatase staining in tumor epithelial, stromal spindle, stromal inflammatory, and normal breast epithelial cells. We found that immunohistochemical staining for aromatase predominated in stromal spindle cells with a median H-score of 13, whereas tumor epithelial, stromal inflammatory, and normal breast elements contained lesser amounts (median H-scores of 4.8, 0.03, and 0.5, respectively). The H-score for stromal spindle cells, but not those for other cell types, correlated highly with the biochemical aromatase assay (P < 0.01). Using a cut-off parameter estimated by a sensitivity/specificity (receiver operating curve) analysis, 62% of tumors were classified as aromatase positive based on stromal spindle cell staining. A similar number were also positive by biochemical assay, with concordance between the two methods of 77%. These observations provide substantial evidence for the presence of aromatase in human breast tumors, particularly in stromal spindle cells, and support the biological importance of aromatase for in situ production of estradiol.

Aromatase↗
PubMed1994

Brain aromatization of androgens.

Although the observation that the brain can form estrogens from androgens was made nearly 25 years ago, the details and implications of this autocrine/paracrine neuroendocrine system are still being discovered. The presence in the brain of the enzyme estrogen synthetase (aromatase) has been documented by biochemical, molecular biologic and morphologic techniques. The system has been shown to be autoregulating--i.e., brain aromatase is induced by the same androgens that it uses as the substrate for the formation of estrogens. Aromatase was first found in the hypothalamus and associated with reproductive neuroendocrine development (the aromatase hypothesis of brain sexual differentiation); however, recent immunohistochemical studies have indicated that aromatase is more widely spread throughout the brain. There apparently are two, separable brain aromatase systems in mammals, a gonad-sensitive hypothalamic system and a gonad-insensitive limbic system. These systems appear during prenatal development and are also found in adults. The aromatase is distributed throughout the neuron, including projective fibers: axons, boutons and synaptic vesicles. Thus, additional actions of locally formed estrogen in these areas of the brain and beyond are likely to be found in the near future.

Aging↗
PubMed1994

Steroid hormones and Tourette's syndrome: early experience with antiandrogen therapy.

We report here the first use in Tourette's syndrome of the nonsteroidal androgen receptor blocking agent flutamide. One man and one woman underwent open trials of the medication, and a second man participated in a placebo-controlled, double-blind crossover trial. Improvement in tic symptoms ranged from 45 to 60%. The improvement was sustained in the woman during daily flutamide use and in one man during its intermittent use. One man's symptoms became refractory to treatment after 5 weeks of flutamide use, whereas the woman became depressed and had protracted diarrhea during her treatment.

Adult↗
PubMed1993

Neural transplantation for neurodegenerative diseases: past, present, and future.

After almost 100 years of sporadic, and marginally successful, studies of neural transplantation in animals, we are now on the threshold of a clinical treatment of the damaged brain. The initial studies of neural transplantation have focused on Parkinson's disease, primarily as a model for a more general strategy of "repair by cellular replacement." Parkinson's is known to result from the loss of a small population of cells that produce the essential neuromodulator, dopamine, for much of the brain. Further, the disease is improved significantly, during the early part of its course, by chemical augmentation of dopamine activity through drug therapies, such as L-dopa. Finally, the disease is often fatal in spite of the best medical treatments, therefore justifying more radical therapeutic experiments. If transplantation of brain cells can be accomplished successfully in humans, as it has been in animals, then replacement of a small population of dopamine-producing cells in Parkinson's disease should have important functional effects and possibly reverse the course and symptoms of the disease. Other useful applications will surely follow for conditions affecting millions of people for whom medicine now has only palliative and ineffective treatments. Just as Parkinson's disease is a model clinical condition for testing cellular replacements, fetal neural tissue transplants are also a first step for a broader strategy of molecular and cellular therapies. Fetal cells are, in many respects, the best replacements one could imagine, since precursor cells have the capacity to develop into every cell found in the adult. So, the best replacement for a dopamine neuron would likely be a precursor dopamine neuron or "neuroblast." Animal research through 1985 had demonstrated the unique properties of such fetal cells, but survivability after transplantation had not been attained with primate or human neural tissue. Our programs developed techniques to transplant monkey fetal neural tissue, to cryopreserve it, and to reverse functional effects of the neurotoxin, MPTP, in monkeys. This technique was applied to the collection and preservation of human tissue, and preliminary successful results have been obtained in patients with idiopathic Parkinson's disease. Others have reported success with different techniques in two MPTP-Parkinsonian patients and a small number of patients with idiopathic disease. If the most dramatic improvements can be replicated consistently and the benefits last for a reasonable period without complications, a clinical treatment might develop using "random-source" fetal cadaver cells.

Animals↗