Biomedical subjects

F Naftolin

Publications and source records attributed to F Naftolin.

At least 199 records · Page 11Linked to original sources

PubMed1987

The ovarian renin-angiotensin system: renin-like activity and angiotensin II/III immunoreactivity in gonadotropin-stimulated and unstimulated human follicular fluid.

Renin-like activity and angiotensin II/III immunoreactivity in follicular fluids from 34 women stimulated with human menopausal gonadotropin and human chorionic gonadotropin (56.8 +/- 6.5 ng angiotensin I per milliliter per hour and 187 +/- 21 pg/ml [mean +/- SEM], respectively) were much higher (p less than 0.001) than in follicular fluids from 12 unstimulated preovulatory women (1.41 +/- 0.37 ng angiotensin I per milliliter per hour and 58.5 +/- 13.7 pg/ml) and in simultaneously drawn plasma (4.47 +/- 0.73 ng angiotensin I per milliliter per hour and 31.8 +/- 11.6 pg/ml, respectively; p less than 0.001). Plasma renin-like activity and angiotensin II/III immunoreactivity in stimulated cycles did not differ from unstimulated cycles. Follicular fluid angiotensin II/III immunoreactivity correlated significantly with follicular fluid renin-like activity in stimulated (r = 0.72; p less than 0.01) and in unstimulated samples (r = 0.86; p less than 0.01). Significant correlation was found also between follicular fluid renin-like activity and estradiol. A sharp preovulatory rise of renin-like activity and angiotensin II/III immunoreactivity was noted in unstimulated follicular fluid samples collected on cycle days 13 and 14 compared to days 9 through 12 (p less than 0.01). The findings that follicular fluid renin-like activity and angiotensin II/III immunoreactivity are correlated, and that gonadotropins have a stimulatory effect on follicular fluid concentrations support our concept of a physiologic intrinsic ovarian renin-angiotensin system.

Angiotensin II↗

PubMed1987

Rapid effects of gonadal steroids upon hypothalamic neuronal membrane ultrastructure.

Freeze-fracture methodology was used to study rat hypothalamic arcuate nucleus (AN) neuronal plasma membrane organization following in vitro perfusion of brain slices with 17-beta-estradiol (17 beta E2) or other test compounds. Physiological levels (10(-10) M) of 17 beta E2 caused an increase in neuronal membrane exo-endocytotic pits within 1 min of perfusion. The increased density of pits was dose related, sustained at a constant rate during 10 min of perfusion, reverted to control values after perfusion with estradiol-free medium for 1 h, and was accompanied by an increased uptake of horseradish peroxidase by the arcuate nucleus in brain slices. The 17 beta E2-induced increase in exo-endocytotic pit density was blocked by tamoxifen (10(-8) M). Cholesterol (10(-10) M), 17-alpha-estradiol (10(-6) M) or dihydrotestosterone (10(-6) M) had no effect on exo-endocytotic pit density. Testosterone had about 50% the potency of 17 beta E2 in increasing exo-endocytotic pit density. These results indicate that physiological levels of 17 beta E2 can have rapid effects upon arcuate nucleus neuronal membrane ultrastructure.

Animals↗

PubMed1987

A hypothesis concerning the general basis of organogenetic congenital anomalies.

Evidence supports the idea that it is the degree of metabolic imbalance present in diabetic gravid women during the period of organogenesis that accounts for organogenetic congenital defects. In light of the proved and inferred metabolic instability occurring during early pregnancy, we propose that metabolic imbalances may occur that result in organogenetic congenital defects in offspring of apparently normal gravid women.

Abnormalities, Multiple↗

PubMed1987

Insulin specific binding sites in the myometrium of pregnant rats.

Insulin (INS) specific binding sites were detected in the myometrium of pregnant rats. The apparent equilibrium dissociation constants for the higher and lower affinity INS binding components were 0.01 X 10(-9) M and 2.5 X 10(-9) M, respectively. During the latter half of pregnancy INS binding increased gradually and peaked on the day of parturition (159.9 +/- 19.8, 196.3 +/- 24.6, 254.7 +/- 36.8, and 272.6 +/- 29.1 and femtomolars per mg protein, mean +/- SEM on days 15, 20, 21, and 22 of gestation, respectively). The pattern of increased INS binding paralleled the prepartum increase in myometrial cell nuclear estrogen receptors as well as myometrial glycogen levels. In contrast, low INS binding was associated with elevated cell nuclear progestin receptor levels, on day 15 and immediately postpartum. These results suggest that, during the latter half of pregnancy, myometrial INS binding capacity and glycogen concentration gradually increase. Since INS receptor levels begin to increase in parallel with increasing nuclear estrogen receptors, INS receptor synthesis may be under estrogen control.

Animals↗

PubMed1987

Immunohistochemical localization of aromatase cytochrome P-450 and estradiol dehydrogenase in the syncytiotrophoblast of the human placenta.

Immunohistochemistry employing immunoglobulin G fractions raised against aromatase cytochrome P-450 and antiserum against 17 beta-estradiol dehydrogenase was used to localize these two steroid-converting enzymes in the human placenta. Immunostaining for both enzymes was found exclusively in the syncytiotrophoblast, while the underlying cytotrophoblast and the villus core did not stain. Ultrastructural examination of aromatase cytochrome P-450- and 17 beta-estradiol dehydrogenase-labeled sections disclosed immunoreactive product in the membranes of the endoplasmic reticulum; the nucleus, mitochondria, Golgi apparatus, and secretory granules were free of staining. These findings suggest that the syncytiotrophoblast is actively involved in the synthesis and metabolism of estrogens and in their role in placental endocrine function.

17-Hydroxysteroid Dehydrogenases↗

PubMed1987

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↗

PubMed1987

In situ hybridization identifies renin mRNA in the rat corpus luteum.

All components of the renin-angiotensin system (RAS), including angiotensinogen messenger RNA (mRNA), renin-like activity (RLA), renin mRNA, angiotensin II (A II) immunoreactivity and angiotensin converting enzyme, have been found in the whole rat ovary and A II receptors have recently been localized to ovarian follicles. Our study was designed to test further which part of the ovary can produce renin. Renin mRNA was detected in the gonadotropin-stimulated rat's corpus luteum using in situ hybridization histochemistry techniques. No positive signal was detected in theca or granulosa cells. These results indicate ovarian renin gene expression in rat luteal cells, where the renin molecule is probably produced, and support our concept of an intrinsic ovarian RAS.

Animals↗

PubMed1986

Use of oral contraceptives by women with epilepsy.

Oral contraceptives have not been associated with exacerbation of epilepsy despite warnings in package inserts. No clinical study has provided scientific evidence of worsening of seizures in epileptic women who use oral contraceptives, and improvement in seizure control has occurred in some cases. The main concern about use of oral contraceptives in this population is their effectiveness in preventing conception. Failure rates are higher in groups of women taking enzyme-inducing antiepileptic drugs. The degree of increased metabolism of estrogen and progestin components is highly variable and unpredictable among individuals. Use of higher doses increases protection against conception but also increases the risk of side effects, particularly in patients in whom no enzyme induction occurs. The strength of hormones in the pill should be selected individually when initiating use. Some women may require higher doses for full contraceptive effect.

Animals↗

PubMed1986

Insulin modulates neuronal plasma membrane development in human fetal spinal cord neurons in culture.

The number of intramembrane protein particles (IMP) in the protoplasmic face of the perikaryal plasma membrane was evaluated in neurons from 9 week-old and 12 week-old human fetal spinal cord in culture. An increased number of IMP was observed in membranes from 12 week-old fetal neurons when compared to membranes from 9 week-old fetal neurons. The addition of insulin (100-2500 microU/ml) to the culture media resulted in a significantly increased number of IMP in neuronal membranes. Incubation with glucose (1.5-6 mg/ml) did not modify the number of IMP and glucose did not potentiate the effect of insulin when both glucose (3 mg/ml) and insulin (500 microU/ml) were added to the culture media. The results suggest that insulin may modulate the development of neuronal membranes and that this effect is not mediated by an increased glucose utilization.

Cell Differentiation↗

PubMed1986

Synaptic remodelling in arcuate nucleus after injection of estradiol valerate in adult female rats.

Adult female rats were injected with a single dose (20 mg/kg) of estradiol valerate (EV). The number of synapses was evaluated in thin sections of arcuate nucleus fixed 3, 8, 16 and 32 weeks after EV treatment and compared with the values obtained in the arcuate nucleus of uninjected proestrus control rats. By 8 weeks after EV treatment a significant (P less than 0.001) decrease was found in the number of axo-somatic and axo-dendritic synapses on dendritic shafts, but not in the number of axo-dendritic synapses on dendritic spines. However, by 32 weeks postinjection, the number of axo-somatic and axo-dendritic synapses had returned to control values. This transient decrease in the number of synapses was preceded by a massive appearance of neuronal degenerative images by 3 weeks after EV injection. These results are interpreted as reflecting a process of circuitry remodelling in the arcuate nucleus after a neuronal lesion induced by estrogen.

Animals↗

PubMed1986

Yolk sac failure in embryopathy due to hyperglycemia: ultrastructural analysis of yolk sac differentiation associated with embryopathy in rat conceptuses under hyperglycemic conditions.

Diabetes mellitus in pregnancy is associated with an increased incidence of various congenital anomalies that occur during organogenesis. Because a well functioning yolk sac is crucial to embryonic growth and development during this period, we performed an ultrastructural study of the effects of excess glucose (total glucose 750 mg/dl, osmolality 305 mOsm/kg) on pregnancy day 10 (Witschi stage 13) rat conceptuses cultured for 48 hr in heat-inactivated male rat serum with and without added d- or l-glucose. Embryos exposed to excess d-glucose demonstrated decreased conceptus size (P less than 0.001), and gross malformations in a dose-related fashion. The visceral yolk sac capillaries and vitelline vessels of conceptuses in excess d-glucose were sparse, patchy, and nonuniformly located. Ultrastructurally, the visceral yolk sac endodermal cells had reduced numbers of rough endoplasmic reticulum, ribosomes, and mitochondria. These obvious defects in yolk sac structure suggest that hyperglycemia during organogenesis has a primary deleterious effect on yolk sac function with resultant embryopathy.

Animals↗

PubMed1986

Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy.

Light microscopic, electron microscopic, and morphometric studies were performed on rat conceptuses cultured between day 10 and day 12 in normal, hyperglycemic, arachidonic acid-supplemented normal, and arachidonic acid-supplemented hyperglycemic rat serum. The results were compared with those of 12-day-old conceptuses grown in utero. No major differences were observed between in vivo and in vitro control conceptuses. Arachidonic acid supplementation of control culture medium resulted in an improvement of conceptus development. Addition of 20 micrograms/ml of arachidonic acid to an otherwise teratogenic hyperglycemic serum medium (950 mg/dl of D-glucose) prevented the malformations induced by hyperglycemic conditions: open neural tube, advanced neuropil formation in the neuroepithelium, significant reduction of rough endoplasmic reticulum, decreased size and number of lipid droplets, and increased number of lysosome-like structures in the visceral endodermal yolk sac cells.

Animals↗

PubMed1986

Neosalpingostomy: comparison of 24- and 72-month follow-up time shows increased pregnancy rate.

Seventy-two patients, 54 for 5 years and 18 for 6 years, were evaluated between 1 and 2 years and 5 and 6 years after bilateral neosalpingostomy. A 27.7% intrauterine pregnancy rate was reported in those patients treated between 1976 and 1978, with a 14% ectopic pregnancy rate. The subsequent 5- to 6-year follow-up study revealed an increase in the pregnancy rate to 41.6% and in the ectopic pregnancy rate to 17.1%. The increase in the pregnancy rate may reflect the ability of the fallopian tube for ciliogenesis and intrinsic repair. Thus if patients have not conceived within 2 years of neosalpingostomy for distal tubal obstruction, significant reproductive potential still exists.

Fallopian Tube Diseases↗

PubMed1986

The association between preovulatory serum 17 beta-estradiol pattern and conception in human menopausal gonadotropin-human chorionic gonadotropin stimulation.

One hundred forty-four women suffering from obstructive tubal disease underwent laparoscopy for in vitro fertilization and embryo transfer (IVF-ET). Ovulation was induced by a human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) protocol. The patients were divided according to their estradiol (E2) response to hMG/hCG administration: group A, an increase of E2 levels on the day after hCG administration (day +1); group B, a decrease of E2 levels on the day after hCG administration. Each of these groups was further subdivided into high responders (E2 greater than 500 pg/ml on day 0), designated A-1 and B-1, respectively, and low responders (E2 less than 500 pg/ml on day 0), designated A-2 and B-2, respectively. Patients responding in an A-1 pattern had significantly higher E2 levels from day 0 to day +8. Fertilization and cleavage rates did not differ among the groups, nor did luteal-phase progesterone. Twenty-one pregnancies were achieved from 126 transfers (17%), of which 16 (75%) occurred in women responding in an A pattern. We recommend that laparoscopy be deferred in women responding with a B pattern, because this preselection may increase pregnancy rates per IVF-ET cycle.

Chorionic Gonadotropin↗

PubMed1986

Monoamine oxidase activity in the term human placenta.

Using a radioenzymatic assay, placental monoamine oxidase (MAO) activity was measured at term after delivery in normal and high-risk pregnancies where decreases in placental blood flow previously were shown. MAO activity in placentas of healthy controls after spontaneous labor was similar to that after elective cesarean section not in labor (mean +/- SE, 133 +/- 18 versus 100 +/- 15 nmol/min/mg protein, respectively). Compared to controls, there was a significant reduction in placental MAO activity in high-risk pregnancies (chronic hypertension, toxemia, and diabetes mellitus), 71 +/- 14, 69 +/- 22, and 69 +/- 7, respectively (P less than 0.05). These differences also were maintained when data were expressed per total placental weight. Effects of antihypertensive drugs on MAO activity in healthy placental tissue were assessed. In homogenates, both hydralazine and magnesium sulfate reduced enzyme activity, while in explants this was not observed. The effects of certain metabolites (which are elevated in plasma of diabetic patients) on healthy homogenates also were studied. Only butyrate reduced enzyme activity. In conclusion, placental MAO activity in vitro is low in term high-risk pregnancies. This may reduce local metabolic inactivation of catecholamines and serotonin and consequently lead to a decrease in blood flow. Such a direct relationship must be confirmed in further studies.

Antihypertensive Agents↗

PubMed1986

Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey.

These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females--one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal--and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with [3H]moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. However, the amygdala, the hippocampus, and several of the cortex samples also contained measurable aromatase complex activity. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex (the dorsolateral-prefrontal, orbital-prefrontal, anterior cingulate, and parietal cortices). The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex.

Animals↗

PubMed1986

Placental and circulating pregnancy-associated plasma protein A concentrates in normal and pathological term pregnancies.

The relationship between placental and peripheral concentrations of pregnancy-associated plasma protein A (PAPP-A) was investigated, using specific radioimmunoassay techniques. At term, placental concentrations of PAPP-A were significantly lower in diabetic pregnancies; 1.9 +/- 0.2 micrograms/mg (mean +/- SE) placental protein as compared with controls (3.2 +/- 0.3). Similar findings were noted when results were analyzed per total placental weight. Patients with classes C-R (1.2 +/- 0.3) had significantly lower PAPP-A levels than in classes A, B (2.4 +/- 0.3 micrograms/mg protein, P = .02). Peripheral PAPP-A levels were measured in patients with chronic hypertension, toxemia, diabetes mellitus, and healthy controls. Overall, the distribution of PAPP-A values in patients with diabetes mellitus were different from controls. In addition, concentrations of PAPP-A in patients with classes B-D were significantly lower than in class A (P less than .001). In patients with chronic hypertension, some values of PAPP-A were lower than the tenth percentile, while patients with toxemia had a distribution which was similar to that of controls.

Diabetes Mellitus↗

PubMed1986

Reproductive failure due to experimentally induced constant estrus does not alter the LH-RH fiber density in the median eminence of the rat.

The effects of anterior hypothalamic deafferentation on luteinizing hormone releasing hormone (LH-RH) fiber density in the mediobasal hypothalamus (MBH) were compared to those of a number of nonsurgical treatments which give rise to anovulatory sterility (injections of estradiol valerate, exposure to constant light, or neonatal androgen administration) in the female rat. All of the treatments used (surgical and nonsurgical) disrupted the normal 4-day pattern of estrous cyclicity. Bilateral anterior hypothalamic deafferentation markedly reduced the packing density of LH-RH fibers in the MBH. Unilateral deafferentation reduced the number of fibers on the ipsilateral side of the MBH by 31-64% and on the contralateral side by 15-40%. In contrast, none of the three nonsurgical treatments had any significant effect on the LH-RH fiber density. Electron microscopic examination revealed no morphologic, or distribution differences in MBH LH-RH fibers between control females and animals rendered anovulatory by the nonsurgical experimental procedures. These results demonstrate that estrogen, androgen, and constant light induced anovulatory sterility are not associated with any overt change in the number or morphology of LH-RH immunoreactive fibers in the MBH, suggesting that the primary lesion responsible for the failure of normal estrous cyclicity in such animals resides in the systems responsible for regulating the activity of the LH-RH neurons rather than in the LH-RH neurons themselves.

Afferent Pathways↗