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Biomedical subjects

A Goldfien

Publications and source records attributed to A Goldfien.

At least 19 recordsLinked to original sources
PubMed1992

The epidemiology of premenstrual symptoms in a population-based sample of 2650 urban women: attributable risk and risk factors.

This epidemiologic survey achieved a reliable measure of the prevalence of premenstrual symptoms by avoiding the biases of small or selected samples, anamnestic error, and subjective expectation. From 6232 women (a 78.8% response), aged 20-49 years, identified through a random sample of urban households, the 24-hour prevalence of symptoms was obtained using the Moos' Menstrual Distress Questionnaire, administered without reference to the menstrual cycle. For 71% of the naturally cycling women, current cycle phase was determined by follow-up (n = 2650); but a higher prevalence of severe or moderately severe affective symptoms in the premenstrual compared to the mid-cycle phase was not found. However, observed risk factor interactions led to the conclusion that premenstrual distress is a discrete mood disorder, affecting women aged 25-35 years, with probable ovulatory cycles, and vulnerable to stress; and that the risk of affective symptoms attributable to the premenstrual state was one percent.

Adult↗
PubMed1992

Cyclic adenosine 3',5'-monophosphate increases beta-adrenergic receptor concentration in cultured human fetal lung explants and type II cells.

cAMP regulates the maturation of many biochemical processes that occur during normal lung development, including the changing levels of surfactant proteins and phospholipids. We examined the effect of cAMP on the beta-adrenergic receptor concentration in the developing human lung. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, increased both the tissue cAMP content and beta-adrenergic receptor concentration in treated explants above those in untreated explants. 8-Bromo-cAMP treatment also elevated the beta-adrenergic receptor concentration of lung explants compared to that in untreated controls. These data indicate the ability of elevated cAMP to increase the beta-adrenergic receptor concentration. Both lung cAMP and beta-adrenergic receptor concentrations increase spontaneously in culture. To test for a possible causal relationship, we cultured explants with protein kinase inhibitors. We found that H-8, a preferential inhibitor of the cAMP-dependent protein kinase [protein kinase-A (PKA)], but not H-7, which inhibits PKA and protein kinase-C with similar potency, blocked the spontaneous rise in beta-adrenergic receptor concentration in human fetal lung explants, indicating that PKA activity is required for this rise in beta-adrenergic receptor concentration. Type II cells isolated from cultured lung treated with H-8 had fewer beta-adrenergic receptors than cells isolated from untreated explants. These studies show that cAMP increases the beta-adrenergic receptor concentration in human fetal lung and specifically in type II cells through a PKA-dependent mechanism, consistent with a role for cAMP in beta-adrenergic receptor regulation during normal lung development.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Exposure of human amnion to amniotic fluid obtained before labor causes a decrease in chorion/decidual prostaglandin release.

Prostaglandin (PG) production by fetal membranes has been implicated in the initiation of human parturition, but its regulation is not well understood. We used an in vitro system to study paracrine control of term, fetal membrane PG production. Using a modified Ussing chamber, full thickness fetal membranes with attached decidua were sealed into a chamber so that each hemichamber was a compartment for either the fetal (amnion) or maternal (chorion/decidua) side. Released PGs from maternal and fetal sides were then measured after exposure of the amnion to either buffer or amniotic fluid. We found that basal release of PGs from both the fetal and maternal sides was 2- to 3-fold higher in membranes obtained after labor compared to those obtained before labor. When amnion obtained after labor was exposed to amniotic fluid, we found a 3- to 5-fold increase in the net release of PGE2 from the amnion; however, the maternal side showed an unexpected relative decrease in PGE2 and PGF2 alpha release. This was a paracrine effect, since direct exposure of chorion/decidua to amniotic fluid caused increased release of the PG precursor, arachidonic acid. Direct transfer of radiolabeled PG from fetal to maternal side was minimal.

Amnion↗
PubMed1991

Cocaine directly augments the alpha-adrenergic contractile response of the pregnant rabbit uterus.

Cocaine use in pregnancy is associated with a premature labor rate as high as 50%, but little is known about its effect on uterine contractility. To determine whether cocaine directly augments pregnant uterus contractility, uterine strips from 27-day pregnant New Zealand White rabbits (term, 31 days) were exposed to cocaine alone (30 mumol/L) or cocaine plus epinephrine (10(-9) to 10(-5) mol/L) or oxytocin (10(-10) to 10(-6) mol/L). Cocaine alone produced no contractions, but increased the epinephrine sensitivity by 51% and the maximal response by 33%. When beta-adrenoceptors were blocked with DL-propranolol (2 mumol/L), the contractile response to epinephrine was increased, and cocaine's effect was blocked. In the presence of the stereoisomer D-propranolol (2 mumol/L) with no beta-adrenergic antagonist activity, the contractile response to epinephrine was unchanged, but the effect of cocaine was still blocked. We conclude that cocaine directly augments the alpha-adrenergic contractile response of the pregnant rabbit uterus by a mechanism that is blocked by the non-beta-adrenergic effects of propranolol.

Adrenergic beta-Antagonists↗
PubMed1991

Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia.

The pregnancy disorder preeclampsia continues as a major cause of maternal and infant mortality and morbidity. Despite intensive research since its recognition 100 years ago, our lack of understanding is evidenced by therapy which remains empiric, early delivery. Part of our failure to more completely understand the syndrome is due to excessive attention to the blood pressure elevation which accompanies the disorder, to the exclusion of a panoply of other physiologic aberrations. Although hypertension, if markedly elevated, can lead to maternal morbidity, it is not usually an important contributor to the pathophysiology of preeclampsia. It is primarily important as a marker for vasoconstriction, which in association with activation of coagulation reduces perfusion to many organs, including the fetal-placental unit. The earliest and likely most important pathophysiologic change is reduced placental perfusion secondary to abnormal implantation and/or a relative increase in placental mass. We propose that reduced placental perfusion results in the production of agent(s) by this organ, which injures or activates endothelial cells. The resulting endothelial cell dysfunction increases sensitivity to normal endogenous pressors, activates the coagulation cascade, and increases vascular permeability. These changes produce the characteristic pathophysiologic changes of the disorder. Evidence supporting this hypothesis includes abnormal endothelial morphology long recognized in glomerular capillaries, increased circulating fibronectin, and increased plasma mitogenic activity that long antedates the clinical disorder. In addition, an agent(s) is present in the blood of these women which activates endothelial cells in vitro as evidenced by increased release of [51Cr] chromium and increased production of PDGF. Preeclampsia is clearly more than "pregnancy induced hypertension."

Endothelium, Vascular↗
PubMed1991

Prostaglandins modulate hormonal effects on rabbit myometrial alpha 1-adrenergic responses.

Estrogen increases the alpha 1-adrenergic contractile sensitivity of the rabbit uterus. Since estrogen treatment increases prostaglandin (PG) production by the perfused rabbit uterus, and PGs contribute to the alpha 1-adrenergic contractile response, we postulated that estrogen's effects on PG production or response may play a role in the increased alpha 1-adrenergic sensitivity induced by estrogen. We studied the effects of the eicosanoid synthesis inhibitor meclofenamate (60 microM) on the response to epinephrine (10(-9)-10(-5) M) of uterine strips from ovariectomized, mature, and estrogen-treated rabbits in terms of both contractile response and PGE2 and PGF2 alpha production. We also measured the contractile response to PGE2 and PGF2 alpha (both 10(-10)-10(-5) M) and KCl (70 mM) of uterine strips from these groups. We found that in the ovariectomized rabbits, meclofenamate decreased PG production, but did not alter the alpha 1-adrenergic sensitivity. In the mature rabbit uterus, meclofenamate decreased both PGE2 and PGF2 alpha production and reduced the alpha 1-adrenergic sensitivity. In the estrogen-treated rabbit uterus, meclofenamate decreased PGF2 alpha, but not PGE2, production and did not alter the alpha 1-adrenergic sensitivity. Finally, meclofenamate reduced the contractile response to KCl in all three groups, and exposure to PGE2 increased the contractile response to KCl in both the mature and estrogen-treated rabbits. We conclude that PGs play a role in the increase in the alpha 1-adrenergic sensitivity of the uterus in mature rabbits, and that this may be the result of an estrogen-mediated alteration in the postreceptor effects of PGs.

Animals↗
PubMed1989

Progesterone prevents linkage of rabbit myometrial alpha 2-adrenergic receptors to inhibition of adenylate cyclase.

The uterine response to adrenergic stimulation is determined by the hormonal milieu. This response is particularly well characterized in the rabbit. In this species, as in humans, the response of the uterus to sympathetic stimulation is alpha-adrenergically mediated contraction with elevated circulating estrogen. However, with progesterone predominance, similar stimulation inhibits uterine contractions, a response mediated by beta-adrenergic receptors acting through their second message, cyclic adenosine monophosphate. We studied the mechanisms by which sex steroids regulate myometrial adrenergic responses. In this study, we questioned whether part of the effect of sex steroids could be explained by an alteration of the coupling of the alpha 2-adrenergic receptor to the inhibition of adenylate cyclase. We found that in the progesterone-treated rabbit, although alpha 2-receptors are present, they are not linked to inhibition of cyclic adenosine monophosphate synthesis. The net synthesis of cyclic adenosine monophosphage in response to endogenous catecholamines is determined by their activation of beta-adrenergic receptors to increase and alpha 2-receptors to decrease cyclic adenosine monophosphate formation. Thus the uncoupling of alpha 2-receptors contributes to increased intracellular cyclic adenosine monophosphate in myometrium of progesterone-treated animals consistent with the reported predominance of beta-adrenergic contractile responses in this setting.

Adenylyl Cyclase Inhibitors↗
PubMed1989

Pulmonary beta-adrenergic receptors and response do not mature precociously in growth-retarded rabbit fetuses.

Growth-retarded infants have a reduced risk of pulmonary morbidity. We used a naturally occurring model of growth retardation in rabbits to test the hypothesis that reduced risk might be related to precocious maturation of the alveolar beta-adrenergic response system in runted neonates. We confirmed that the weights of the fetuses were significantly different, depending on uterine position, as predicted by this model. However, we found no evidence of either increased beta-adrenergic receptor concentration or cyclic adenosine monophosphate generation in the smaller fetuses. These results indicate that reduced fetal size in this model of growth retardation does not result in accelerated maturation of alveolar beta-adrenergic responses in neonates.

Animals↗
PubMed1989

Hormonal regulation myometrial adrenergic responses: the receptor and beyond.

The contractile response of the uterus is modified by sex steroids. In rabbit uterus, oestrogen promotes alpha-adrenergically-mediated contraction, whilst progesterone treatment results in beta-adrenergic relaxation. Examination of the mechanisms responsible for these changing adrenergic responses with sex steroids reveals multiple sites of regulation. Oestrogen increases alpha 1-receptor concentration and the linkage of the receptor to phospholipase C. In addition to this direct effect to promote contraction, oestrogen also uncouples the beta-receptor from adenylate cyclase. Progesterone, conversely, promotes relaxation through beta-receptors by uncoupling alpha 2-receptors from inhibition of adenylate cyclase. Thus sex steroids can regulate specific agonist responses at and beyond the receptor.

Adenylyl Cyclases↗
PubMed1988

Alpha adrenergic stimulation reduces cyclic adenosine 3',5'-monophosphate generation in rabbit myometrium by two mechanisms.

Rabbit myometrium contains postsynaptic alpha-1, alpha-2, and beta-2 adrenoreceptors. The response to endogenous catecholamines depends on the summation of interactions at these receptors and is influenced by the hormonal environment. Estrogen treatment of ovariectomized rabbits increases the alpha adrenergic contractile response whereas progesterone treatment of estrogen primed animals results in a predominance of the beta adrenergic response, which is inhibition of contractions. Of the receptor subtypes, only the alpha-2 receptor concentration is increased at physiological estrogen concentrations. However, alpha-2 receptors have not been shown to be directly involved in myometrial contraction, which appears to be mediated solely by alpha-1 adrenergic interactions. To test whether alpha-2 receptors might indirectly affect contraction by opposing interactions at the beta receptor, we examined the ability of alpha adrenergic stimulation to reduce myometrial cyclic adenosine 3',5'-monophosphate (cAMP) generation. We find that alpha-2 receptors inhibit myometrial ade adenylate cyclase through the guanine nucleotide regulatory protein, Gi. In addition, we find that activation of alpha-1 receptors also reduces cAMP generation. This interaction, which can be demonstrated in the absence but not the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, does not appear to be mediated through Gi. These findings illustrate the complexity of adrenergic interactions in tissues containing several adrenergic subtypes.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Estrogen reduces beta-adrenoceptor-mediated cAMP production and the concentration of the guanyl nucleotide-regulatory protein, Gs, in rabbit myometrium.

The uterine contractile response to adrenergic agonists or sympathetic stimulation is influenced dramatically by the hormonal milieu. Rabbit uterine contraction is mediated by alpha 1-adrenoceptors, whereas relaxation in response to the same stimulus is mediated by beta 2-adrenoceptors. Whether uterine contractility is increased or decreased by adrenergic stimulation is determined by the gonadal steroids estrogen and progesterone: uterine contraction prevails in the estrogen-dominant or the ovariectomized animal, but in the progesterone-dominant rabbit, uterine relaxation is observed. In previous studies, we have demonstrated that changes in the concentration or agonist affinity of these adrenoceptors cannot account for the changes in contractile response. In the present studies, we tested whether sex steroids might alter beta-adrenergic response by acting on events distal to receptor occupancy, and whether this could explain the conversion of contractile response. We found that myometrial cAMP generation is potently stimulated by beta-agonists in progesterone-treated and also in ovariectomized animals, but this stimulation is absent after estrogen treatment. Similar, but smaller, changes were observed for cAMP generation in response to prostaglandin E2 and forskolin. Stimulation of adenylate cyclase in uterine particulates by agents which act on the guanyl nucleotide-sensitive stimulatory transducer, Gs, is unchanged after estrogen treatment. However, specific labeling of Gs catalyzed by cholera toxin is reduced in membrane particulates from estrogen-treated animals. Recombination of extracts of uterine membranes from the differently treated animals also suggested qualitative differences in Gs. We conclude that at least one component of the adenylate cyclase cascade beyond the beta-adrenoceptor, i.e., Gs, is a target for ovarian steroids; estrogen reduces Gs labeling and beta-adrenoceptor-mediated cAMP production. However, uterine Gs labeling and cAMP production are similar in ovariectomized and in progesterone-treated rabbits. Since these uteri exhibit different contractile responses, the observed changes are not sufficient to explain sex steroid-mediated conversion of myometrial contractile response.

Adenosine Diphosphate Ribose↗
PubMed1987

Estrogen increases adrenergic- but not cholinergic-mediated production of inositol phosphates in rabbit uterus.

alpha 1-Adrenergic and muscarinic cholinergic stimuli activate uterine contraction. Estrogen increases adrenergic but not cholinergic sensitivity of rabbit myometrium independent of its effects on adrenoceptor concentration. Since both alpha 1-adrenergic and muscarinic receptors are coupled to phosphatidylinositol hydrolysis, we tested the hypothesis that estrogen increases adrenergic- but not cholinergic-mediated inositol triphosphate production. We found that maximal production of inositol phosphates stimulated by norepinephrine was increased approximately 3-fold following estrogen treatment. Cholinergic-stimulated production was not increased by estrogen treatment. These results demonstrate that the effect of estrogen to enhance uterine adrenergic sensitivity is associated with an increased post-receptor response. The nature of the selectivity of estrogen for adrenergic versus cholinergic response remains obscure, but the results suggest the presence of parallel pathways for receptor activation of a common post-receptor response.

Animals↗
PubMed1987

Rabbit myometrial adrenergic sensitivity is increased by estrogen but is independent of changes in alpha adrenoceptor concentration.

The ability of estrogen to increase the alpha-1 adrenergic sensitivity of rabbit uterine smooth muscle was compared with its effects on the concentration of alpha adrenoceptor subtypes in myometrium. Compared to ovariectomized controls, estrogen treatment was found to increase the adrenergic contractile sensitivity of rabbit uterus determined in vitro. Estrogen treatment increased uterine alpha-2 adrenoceptor concentration nearly 5-fold. Mature rabbits (endogenous estrogen) had the same uterine sensitivity and alpha-2 adrenoceptor concentration as estrogen-treated rabbits. Alpha-1 receptor concentration was increased only in the estrogen-treated group, and was accompanied by increased maximal contractile response. Thus, the increase in adrenergic sensitivity after estrogen was correlated closely with an increased concentration of alpha-2 adrenoceptors. However, enhanced adrenergic sensitivity persisted after alpha-1 and alpha-2 receptor concentration returned to pre-estrogen levels in rabbits pretreated with estrogen before ovariectomy. Studies utilizing subtype-selective competitive antagonists verified that contractile response is mediated primarily by alpha-1 adrenoceptors, with no apparent influence of alpha-2 adrenoceptors. Finally, we found that adrenergic sensitivity is altered by temperature and divalent cation concentration, but these effects do not prevent the expression of the regulatory action of estradiol. We conclude that estrogen increases the alpha-1 adrenergic sensitivity of rabbit uterus without changes in alpha-1 receptors, and thus may act on postreceptor response events.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Rabbit uterine oxytocin receptors and in vitro contractile response: abrupt changes at term and the role of eicosanoids.

We examined the relation between increased uterine oxytocin receptor concentration and increased in vivo sensitivity of the rabbit uterus to oxytocin at the end of gestation. We determined oxytocin receptor concentrations in myometrium and decidua on different days near term of gestation and postpartum. We also examined the in vitro contractile response to oxytocin on days 30 and 5 days postpartum, when the uterus is unresponsive in vivo, and on day 31 (term), when the uterus is exquisitely sensitive to this hormone in vivo. In addition, we tested the role of endogenous eicosanoids and decidual oxytocin receptors in the myometrial contractile response to oxytocin by examining the contractile response in the presence of the cyclooxygenase/lipoxygenase inhibitor sodium meclofenamate or in muscle strips from which the decidua had been removed by scraping. The concentration of specific binding sites for [3H]oxytocin in myometrial and also decidual membrane preparations was determined. We demonstrate that contractile sensitivity to oxytocin increases at least 4-fold between days 30 and 31 (term) of gestation, and this is accompanied by a nearly 10-fold increase in the concentration of oxytocin-binding sites in both decidua and myometrium. The lesser sensitivity to oxytocin on day 30 was, however, only apparent in the presence of meclofenamate, which suggests that endogenous eicosanoids contribute to the preterm response to oxytocin measured in vitro. The maximal response to oxytocin (integrated area) increased 2-fold between day 30 and term. Thus, an increase in both sensitivity and maximal response to oxytocin could be demonstrated at term in vitro. Five days after parturition, maximal response and uterine sensitivity measured in the presence of meclofenamate had returned to those of the preterm uterus, and the concentration of oxytocin-binding sites had declined. In contrast, sensitivity and maximal response to the cholinergic agonist carbamylcholine declined between day 30 and term. These results support a highly regulated physiological role for oxytocin in parturition which depends primarily on changes in receptor concentration.

Animals↗
PubMed1977

Identification of beta-adrenergic binding sites in rabbit myometrium.

Rabbit uterine muscle may contract or relax with adrenergic stimulation depending on the hormonal milieu. This difference in contractile activity has been shown to be due to alteration of adrenergic response between alpha-adrenergic (contraction) and beta-adrenergic (relaxation). When rabbits are treated with estrogen followed by progesterone, norepinephrine produces myometrial relaxation. This effect is blocked by propranolol, indicating that it is mediated by beta receptor activation. A subcellular preparation of this myometrium has adenylate cyclase activity that can be stimulated by isoproterenol + guanyl-5'-yl-imidodi-phosphate (Gpp(NH)p). The radioligand [125I]iodohydroxybenzylpindolol binds to the same preparation. The binding is rapid, 80% maximal in 10 min, and readily reversible (t1/2 = 5 min). The binding is high affinity (Kd = 0.12 nM), low capacity (15 fmol/mg protein), and is to a single class of binding sites. Binding is competed for stereoselectively by beta adrenergic agonists and antagonists. The competition of beta adrenergic agonists for binding, isoproterenol = ritodrine greater than epinephrine greater than norepinephrine, is consistent with interactions at a beta2-adrenergic receptor.

Adenylyl Cyclases↗