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F Naftolin

Publications and source records attributed to F Naftolin.

At least 163 records · Page 9Linked to original sources
PubMed1990

Comparison of age- and sex-related changes in cell nuclear estrogen-binding capacity and progestin receptor induction in the rat brain.

Previous studies have suggested parallels between the mechanisms underlying sexual differentiation and age-related loss of reproductive cyclicity in the female rat. Both appear to involve the actions of estrogen on the brain and are associated with a reduction in hypothalamic estrogen sensitivity. In this study the effects of sex and aging on cell nuclear estrogen receptor-binding capacity and cytosol progestin receptor induction in the pituitary gland, periventricular preoptic area (PVP), medial preoptic area (mPO), bed nucleus of the stria terminalis, arcuate median eminence region (ARC), ventromedial nucleus (VMN), and corticomedial amygdala were directly compared. Young (2.5 months old) and middle-aged (8-10 months old) male and female and old (19 months old) female rats were gonadectomized 14 days before adrenalectomy (ADX). For comparison of cell nuclear estrogen receptor-binding capacity, animals received a saturating dose of estradiol (36.0 micrograms/kg BW) 3 days after ADX and 1 h before death. Cell nuclear estrogen binding was measured by an in vitro exchange assay. For comparison of estrogen-induced progestin receptors, animals received a sc placed Silastic capsule containing 10% 17 beta-estradiol at the time of ADX and were killed 3 days later. Cytosol progestin binding was measured by an in vitro binding assay. Cell nuclear estrogen-binding capacities and cytosol progestin receptor induction were lower in the PVP, mPO, and VMN of the young male than in the young female. In the female, the level of progestin receptor induction in the pituitary and brain was unaffected by age; however, cell nuclear estrogen-binding capacity in the mPO, VMN, ARC, and pituitary gland was lower in old than in middle-aged females. These results demonstrate that the effects of sexual differentiation and aging on the hypothalamus involve similar, but not identical, region-specific reductions in cell nuclear estrogen receptor-binding capacity. The consequences of these reduced estrogen receptor binding levels in terms of the induction of progestin receptor in response to estrogen exposure are, however, very different in the male compared to those in old female rats.

Adrenalectomy↗
PubMed1990

Luteal rescue in in vitro fertilization-embryo transfer.

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.

Adult↗
PubMed1989

Estradiol induces rapid remodelling of plasma membranes in developing rat cerebrocortical neurons in culture.

Exo-endocytotic images and intramembrane particles were quantitatively assessed in freeze-fracture replicas from the plasma membrane of dispersed fetal rat cortical neurons (day 16 gestation) grown for 24 days in culture. The addition of 10(-10) M 17 beta-estradiol to the culture medium resulted in a significant increase in the numerical density of exo-endocytotic images within 1 min. A further increase of the number of exo-endocytotic images associated to a significant decrease in the number of intramembrane particles was observed in cells exposed for 10 min to 17 beta-estradiol. Similar results were observed when the cells were exposed to 17 beta-estradiol for 17 days. No effects on exo-endocytotic images and intramembrane particles were observed when 17 alpha-estradiol was added, instead of 17 beta-estradiol, to the cultures. These results indicate that physiological levels of 17 beta-estradiol can have rapid effects upon the ultrastructure of the neuronal membrane of developing cerebrocortical neurons.

Animals↗
PubMed1989

Astrocytic shape and glial fibrillary acidic protein immunoreactivity are modified by estradiol in primary rat hypothalamic cultures.

Primary cultures from fetal rat hypothalamus (embryonic day 15-16) were grown for 9 days in a serum-free medium and then fixed and immunostained for glial fibrillary acidic protein (GFAP). The majority of the GFAP-immunoreactive astrocytes were flat, polygonal, without processes and showed a low intensity immunoreactivity which was restricted to the perinuclear region. Elongated, process-bearing astrocytes, with an intense immunoreactivity in the soma and processes, were also observed in a smaller proportion (30%). Addition of estradiol (10(-12) to 10(-8) M) to the culture medium 24 h before GFAP immunostaining resulted in an increased proportion (59-69%) of process-bearing, intense immunoreactive cells. This effect was blocked by tamoxifen (10(-8) M). The total number of GFAP-immunoreactive astrocytes was not modified by estrogen or tamoxifen. These results indicate that estradiol may modulate the cell shape and the distribution of GFAP in astrocytes in culture and suggest that astrocytes can be a target for sex steroids during development of the central nervous system.

Animals↗
PubMed1989

Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer. A prospective randomized trial.

One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.

Adult↗
PubMed1989

Immunohistochemical localization of renin and angiotensin II in human ovaries.

Ovaries from six women with normal menstrual cycles, a follicle wall biopsy specimen from a gonadotropin-stimulated preovulatory ovary, and a corpus luteum of pregnancy were examined by immunohistochemistry for the presence of immunoreactive renin and angiotensin II. Both antisera densely stained thecal and stromal cells (interstitial complex) and luteal cells. Whereas granulosa cells in developing follicles were either unstained or lightly stained, the heavily luteinized granulosa cells of the preovulatory stimulated follicle were strongly positive for immunoreactive renin and angiotensin II. These anatomic findings are consistent with gonadotropin-stimulated local production of both renin and angiotensin II in the human ovary and support the functional roles proposed for the ovarian renin-angiotensin system in follicle development, ovulation, and luteal function and during pregnancy.

Adult↗
PubMed1989

Immunoregulatory activity in supernatants from cultures of normal human trophoblast cells of the first trimester.

Supernatants from isolated trophoblast cell cultures (trophoblastic fluid) derived from first-trimester human placentas were assessed for immunoregulatory activity. Trophoblastic fluid at different days of culture consistently inhibited the blast transformation of allogenic lymphocytes. This suppressor effect had no apparent correlation with biosynthesis of human chorionic gonadotropin by trophoblast cells, since this hormone was secreted into the culture fluid only for the initial 3 days. However, the culture fluids of such purified trophoblast cells contained an immunosuppressive factor, pregnancy-associated plasma protein A, which was measurable throughout the culture period of 8 days. The presence of pregnancy-associated plasma protein A in significant amounts in trophoblastic fluid collected at daily intervals indicated a continuous secretion ability of pregnancy-associated plasma protein A by trophoblast cells in culture parallel to the suppressive immunoregulatory effect of the fluid. Such immunosuppressive effect was absent in the culture fluids of control BeWo malignant trophoblast cells; the BeWo cell culture fluids had markedly reduced levels of pregnancy-associated plasma protein A. The culture supernatant of normal trophoblast cells of placentas from first-trimester pregnancy activated in vitro the generation of a population of suppressor lymphocytes. This effect is generally considered responsible for immunologic tolerance. Therefore demonstration of immunosuppressive effects and the presence of relatively high levels of pregnancy-associated plasma protein A in trophoblastic fluid indicate that such proteins secreted by the trophoblast cells may be important in the local immunoregulatory processes of the fetal allograft.

Cells, Cultured↗
PubMed1989

Synaptic remodeling in the rat arcuate nucleus during the estrous cycle.

Adult female rats showing regular vaginal cycles were studied in order to determine the number of axosomatic synapses in thin sections of the arcuate nucleus. The number of synapses per length of perikaryal membrane was significantly decreased in estrus, compared to other days of the estrous cycle (P less than 0.05). The reduction in the number of synapses in estrus was accompanied by a decrease in the percentage of the average length of perikaryal membrane covered by presynaptic terminals and by an increase in the percentage of membrane in close apposition of glial processes. Since the average perikaryal perimeter was not significantly changed during the estrous cycle, these results indicate a net decrease in the number of arcuate nucleus axosomatic synapses between proestrus and estrus, with a reinnervation of arcuate neurons between estrus and metestrus. These results suggest that there is a physiological synaptic turnover in the arcuate nucleus of the rat during the estrous cycle.

Animals↗
PubMed1989

Sex differences in plasma membrane concanavalin A binding in the rat arcuate neurons.

Previous studies have shown that synaptic connections and organization of neuronal membranes are sexually dimorphic in the arcuate nucleus of developing and adult rats. These sex differences can be abolished by the perinatal androgenization of females. In this study the label-fracture method of Pinto da Silva and Kan was used in order to determine whether membrane sex differences are related to the glycoconjugates in neuronal plasma membranes. Six Sprague-Dawley female rats treated with testosterone on the day of birth, six control females injected with vehicle and six intact males were studied when they were 100 days old. The arcuate nucleus was dissected and incubated for 2 hours in a solution of 0.25 mg/ml concanavalin A, washed in buffer and incubated for 3 hours in a suspension of horseradish peroxidase-coated colloidal gold. Then, freeze-fracture replicas of the arcuate nucleus were prepared. Colloidal gold labeling was observed to be codistributed with intramembrane particles in the outer membrane face of the neuronal perikaryal plasma membrane. The numerical density of small (less than 10 nm) intramembrane particles and colloidal gold particles was significantly greater in control female membranes when compared to males or to androgenized females. The labeling was significantly reduced when the arcuate nucleus was incubated with concanavalin A in presence of 0.5 M methyl-alpha-manopyranoside. These findings indicate a sex difference in the density and distribution of glycoconjugates and intramembranous particles in the neuronal plasma membrane that is dependent on the perinatal levels of sex steroids and is concordant with, and could be the cause of, sex differences in the pattern of synaptic contacts.

Animals↗
PubMed1989

Growth promoting effects of IGF-I on fetal hypothalamic cell lines under serum-free culture conditions.

Recent evidence indicates that the insulin-like family of peptides may act as endogenous trophic factors in the central nervous system. To further examine this possibility we have investigated the effects of three insulin-like peptides on the in vitro growth of fetal hypothalamic cell lines. Two virally transformed rat hypothalamic cell lines which have been developed in our laboratory (A-6 and F-12) were used. Cells were plated at varying densities and cultured in the presence or absence of either insulin-like growth factor I (IGF-I), insulin, or multiplication stimulating activity (MSA or IGF-II), in serum-free medium for 1 wk. Cell growth was assessed by counting or by measuring cellular incorporation of 3H-thymidine. Of the three peptides tested IGF-I was the most potent in eliciting cell growth. Insulin also stimulated growth of both cell lines, but was 100 times less potent for A-6 cells while it was equipotent with IGF-I in F-12 cells. MSA had no effect on either cell line. Both IGF-I and insulin showed dose-response effects in increasing cell growth. We also found that the two cell lines had the greatest response to IGF-I at low cell densities. Finally, time-course experiments suggested that a continued presence of the peptide is essential for the growth-promoting effects. We conclude that IGF-I is a potent growth factor for virally transformed cell lines derived from the rat fetal hypothalamus. Since both IGF-I immunoreactivity and IGF-I receptors have been located in this diencephalic area these results suggest that IGF-I may constitute a mitogenic signal for hypothalamic cells during neurogenesis.

Animals↗
PubMed1989

Yolk sac failure in embryopathy due to hyperglycemia: horseradish peroxidase uptake in the assessment of yolk sac function.

We described previously the morphologic alterations of the visceral endodermal yolk sac cells of rat conceptuses cultured under hyperglycemic conditions which occurred concomitantly with major embryonic malformations. To determine whether the transport function of the yolk sac was impaired simultaneously as a result of these hyperglycemic conditions, horseradish peroxidase was used as a tracer protein to assess the transport function of the visceral endodermal yolk sac cells of conceptuses cultured in both control and hyperglycemic media. Cellular uptake of peroxidase, which was added to the culture medium for 3 or 24 hours, was observed in controls. This differed from the marked diminution in peroxidase uptake seen in conceptuses cultured in hyperglycemic medium. These results demonstrate that during hyperglycemia-induced embryopathy, there is concomitant yolk sac failure evidenced by morphologic alterations and impaired endocytosis. These findings therefore strengthen our hypothesis that diabetes-related malformations, as demonstrated experimentally in rat conceptuses, are associated with impairment in the structure and functions of the visceral yolk sac cells during a critical period of organogenesis.

Animals↗
PubMed1988

Cryopreservation, culture, and transplantation of human fetal mesencephalic tissue into monkeys.

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

Animals↗
PubMed1988

Sexual differentiation of the neuronal plasma membrane: neonatal levels of sex steroids modulate the number of exo-endocytotic images in the developing rat arcuate neurons.

Exo-endocytotic images and intramembrane protein particles (IMP) were quantitatively assessed in freeze-fracture replicas from the plasma membrane of arcuate neurons of rats aged 0 (newborns), 10, 20 and 100 days postpartum. Membranes contained significantly (P less than 0.02) more IMPs in females than in males. Exo-endocytotic images were increased in newborn and 10-day-old males when compared to adult males or to developing females (48 +/- 6 vs 6 +/- 1 images/100 micron 2 in 10-day-old male and female rats, respectively). Androgenization of females with a single injection of testosterone propionate on the day of birth resulted in an increased number of exo-endocytotic images in developing animals (75 +/- 9 images/100 micron 2, 10-day-old rats) and in the abolishment of the sex differences in the number of IMPs.

Aging↗
PubMed1988

Blockage of ovulation by an angiotensin antagonist.

Angiotensin II (Ang II) is present in high concentrations in preovulatory follicular fluid, and ovarian follicular cells have specific Ang II receptors. To investigate the possible direct involvement of Ang II in ovulation the specific receptor antagonist of Ang II, saralasin, was administered by intraperitoneal injection to immature rats in which follide development and ovulation had been induced with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG), respectively. Saralasin halved the number of oocytes found in the fallopian tubes 17 to 20 hours after administration of hCG. The antiovulatory effect was observed when saralasin was given 1 hour before hCG or 1 or 3 hours after hCG but not when given 5 hours after hCG. Simultaneous administration of Ang II reversed the saralasin blockage of ovulation. These results indicate a direct, obligate role for Ang II in ovulation and raise the possibility of contraceptive and profertility applications for agonists or antagonists of the renin-angiotensin system that are aimed at the ovulatory process.

Angiotensin II↗
PubMed1988

Immunohistochemical evidence for synaptic connections between pro-opiomelanocortin-immunoreactive axons and LH-RH neurons in the preoptic area of the rat.

Connections between adrenocorticotropic hormone (ACTH)-immunoreactive neurons in the arcuate nucleus and the preoptic area were studied in the female rat. ACTH-immunopositive terminals were observed in the medial preoptic area in contact with dendritic shafts, while in the ventrolateral preoptic area the majority of ACTH-immunoreactive synapses were found on dendritic spines. Double-label electron microscopic immunocytochemistry using peroxidase and avidin-ferritin as contrasting electron-dense markers revealed numerous synaptic contacts between ACTH-immunopositive boutons and luteinizing hormone-releasing hormone (LH-RH)-immunoreactive dendritic shafts in the medial preoptic area. Following injection of horseradish peroxidase (HRP) into the medial preoptic area, retrogradely HRP-labeled perikarya were observed throughout the arcuate nucleus. Double-staining experiments revealed that a proportion of these retrogradely labeled cells, in the ventromedial arcuate nucleus, are also immunoreactive for ACTH. These results suggest that pro-opiomelanocortin peptide-producing neurons in the ventromedial arcuate nucleus project to the medial preoptic area. Some of these neurons establish direct synaptic contacts with LH-RH-immunoreactive cells.

Adrenocorticotropic Hormone↗
PubMed1988

Immunocytochemical evidence for direct synaptic connections between corticotrophin-releasing factor (CRF) and gonadotrophin-releasing hormone (GnRH)-containing neurons in the preoptic area of the rat.

Electron microscopic double-label immunostaining with peroxidase and avidin-ferritin was used to study connections between corticotrophin-releasing factor (CRF) and gonadotrophin-releasing hormone (GnRH) immunoreactive elements in the medial preoptic area of the rat. Synaptic contacts were observed between CRF-immunoreactive axon terminals and the dendrites of GnRH-immunopositive neurons. These results suggest that the inhibitory effects of stress-induced CRF release on reproductive function may involve a direct CRF input to the GnRH-producing cells.

Animals↗