PubMed Health⌕ Search

Biomedical subjects

H H Feder

Publications and source records attributed to H H Feder.

At least 37 records · Page 2Linked to original sources
PubMed1989

Inhibition of guinea pig lordosis behavior by the phenylethanolamine N-methyltransferase (PNMT) inhibitor SKF-64139: mediation by alpha noradrenergic receptors.

Experiments were undertaken to determine whether the steroid-dependent lordosis response of female guinea pigs is under adrenergic control. In initial experiments, treatment with the centrally active phenylethanolomine N-methyltransferase (PNMT; the enzyme catalyzing methylation of norepinephrine to epinephrine) inhibitor SKF-64139 inhibited lordosis behavior induced by estradiol-17 beta benzoate plus progesterone. SKF-29661, a PNMT inhibitor that does not cross the blood-brain barrier, did not affect lordosis. However, no detectable epinephrine was found in brain or spinal cord of drug- or vehicle-treated guinea pigs. This suggests that epinephrine neuronal systems do not exist in the guinea pig CNS. In agreement with this idea, the inhibitory effects of SKF-64139 on lordosis were found to be primarily attributable to the blockade of alpha noradrenergic receptors rather than to PNMT inhibition. Two lines of evidence support this conclusion. First, using in vitro receptor binding techniques, SKF-64139 was found to have a relatively high affinity for alpha 1 and particularly alpha 2 receptors in guinea pig forebrain. Second, presumably through competitive inhibition of SKF-64139 binding to alpha receptors, treatment with clonidine (an alpha receptor agonist) overrode the inhibitory effects of SKF-64139 on lordosis. Taken together, these findings indicate the possible absence of epinephrine neuronal systems in guinea pig brain and reemphasize the importance of alpha receptors in regulating steroid-dependent lordosis behavior in this species.

Animals↗
PubMed1989

Alpha 1 noradrenergic antagonism decreases hormonally-induced and hormonally-independent lordosis.

Manipulations of the alpha noradrenergic (NE) system affect both lordosis and the concentration of hypothalamic steroid receptors. The present studies explored whether NE affects lordosis in guinea pigs via changes in hypothalamic estrogen or progestin receptors or through some other mechanism. The alpha 1 NE antagonist prazosin blocked lordosis which was induced with estradiol benzoate (EB) followed by progesterone (P), lordosis which was induced by EB alone and lordosis which is not dependent upon gonadal hormones for its display. These results suggest that NE modulation of lordosis in the guinea pig is not exerted solely through progestin receptors or estrogen receptors. Because prazosin blocked hormonally-independent lordosis, it is apparent that the NE system modulates some nonhormonal component of lordosis in guinea pigs.

Animals↗
PubMed1989

Different roles of alpha-noradrenergic receptor subtypes in regulating lordosis.

Ovariectomized guinea pigs were given free estradiol (E) at hr 0 and 28, and progesterone (P) at hr 39. Experiment 1: The alpha-1 noradrenergic antagonist prazosin, but not the alpha-2 noradrenergic antagonist idazoxan, prevented display of lordosis behavior when administered systemically 30 min prior to E injections at either hr 0 or 28, or 30 min prior to both injections. Experiment 2: Multiple injections of idazoxan (i.e., 30 min prior to and 60 and 120 min after each E injection) failed to prevent display of lordosis. Experiment 3: E-primed animals were given a single injection of idazoxan 1 hr before P, or 5 hr after P. In those animals given idazoxan 1 hr before P, display of lordosis was not prevented. However, in animals given idazoxan once lordosis display had begun (i.e., 5 hr after P) ongoing lordosis behavior was blocked. These data suggest differential roles of alpha-noradrenergic receptor subtypes in regulation of lordosis: noradrenergic transmission through the alpha-1 subtype may mediate hormone-priming processes leading to lordosis, whereas transmission through the alpha-2 subtype may modulate ongoing lordosis responses.

Adrenergic alpha-Antagonists↗
PubMed1988

Alpha 1- and alpha 2-noradrenergic receptors in steroid-sensitive brain areas: development and response to estradiol-17 beta benzoate in neonatal guinea pigs.

Immature female guinea pigs are relatively insensitive to the effects of ovarian steroids on certain reproductive processes including the facilitation of sexual receptivity and the induction of hypothalamic progestin receptors by estrogen. In adult guinea pigs, alpha-receptor-mediated noradrenergic transmission is known to affect both of these processes. In the experiments reported here, we investigated the possibility that age-related differences in alpha 1- and alpha 2-noradrenergic receptors might underlie the insensitivity of neonates to ovarian steroids. With tritium-sensitive film autoradiography, the distribution of alpha 1- and alpha 2-receptors in neonatal and adult female guinea pigs was compared and the effects of exogenous estradiol-17 beta on alpha-receptor binding was examined in neonatal guinea pigs. The results of these experiments showed that in animals not treated with estrogen the binding of both alpha-receptor subtypes differed between adults and neonates in several brain regions including areas known to be involved in the regulation of reproduction. In all regions where differences occurred, alpha-receptor levels were higher in neonatal females than in adult females. In addition, in contrast to previously reported results in adults, estrogen did not affect alpha-receptor binding in any region of neonatal guinea pig brain.

Animals↗
PubMed1988

Sex differences in nuclear androgen receptors in guinea pig brain and the effects of an alpha 2 noradrenergic blocker on androgen receptors.

The binding of the synthetic androgen, [3H]methyltrienolone (R1881) to nuclear androgen receptors (NAR) was studied in various brain areas of gonadectomized male and female guinea pigs treated for 3 days with 2 mg testosterone propionate. The Scatchard analysis of salt-extracted NAR showed a single, high-affinity receptor with a Kd of 0.152 nM and maximum binding sites (Bmax) of 161.9 fmol/mg DNA. The concentration of NAR was highest in the hypothalamus (HYPO) and preoptic area (POA) in both males and females. Lower receptor levels were detected in the amygdala and cortex. NAR levels were significantly lower in the POA of females than in males. Systemic injection of prazosin, an alpha 1-adrenergic antagonist had no effect on NAR concentrations, but an alpha 2-antagonist, idazoxan, significantly reduced the binding of [3H]R1881 to NAR in both HYPO and POA. The reduction in binding of the ligand to receptor was not due to alterations in affinity of NAR, but rather to the decline in the number of receptors.

Adrenergic alpha-Antagonists↗
PubMed1988

Alpha 1- and alpha 2-noradrenergic receptor binding in guinea pig brain: sex differences and effects of ovarian steroids.

Noradrenergic transmission mediated by alpha 1-receptors is involved in the regulation of ovarian steroid-dependent reproductive processes in female guinea pigs. In addition, estradiol treatment is known to affect alpha 2-receptor binding in some steroid-sensitive regions of guinea pig brain. In these experiments, we further assessed the effects of ovarian hormones on alpha-noradrenergic receptors with quantitative autoradiographic methods. Binding of alpha 1- and alpha 2-noradrenergic receptors was measured in male and female guinea pigs treated with either estradiol or oil to determine if sex differences in steroid sensitivity might be related to differences in the distribution or modulation of alpha-receptors. In a second experiment, the possibility was tested that progesterone might alter the sensitivity to norepinephrine by modulating alpha 1- or alpha 2-receptor binding in estradiol-primed female guinea pigs. Results of these studies showed that estradiol treatment reduced alpha 1- and alpha 2-receptor binding of the ventromedial hypothalamic nucleus only in females and increased alpha 2-receptor binding in several preoptic nuclei of both sexes. Progesterone administration, however, had no effect on either alpha-receptor subtype. These studies indicate that estradiol-induced changes in alpha-receptor binding might be involved in steroid-dependent reproductive processes and in the differential responsiveness of males and females to ovarian hormones. Changes in these receptors do not appear to be involved in the stimulatory effects of progesterone on neuroendocrine processes.

Animals↗
PubMed1988

Facilitation of lordosis in guinea pigs by an alpha-noradrenergic agonist is independent of progestin receptor stimulation.

Because manipulations of the noradrenergic system affect both lordosis behavior and progestin receptor levels in female guinea pigs, the present study attempted to determine if the noradrenergic (NE) system affects lordosis solely because of its impact on progestin receptors. Although the progestin receptor antagonist RU486 significantly reduced progesterone-facilitated lordosis, it had no effect on lordosis induced by the alpha-NE agonist clonidine in estrogen-primed female guinea pigs. This indicates that although progesterone may facilitate lordosis in female guinea pigs via activation of progestin receptors, the alpha-noradrenergic agonist clonidine does not mediate lordosis through the same mechanism.

Animals↗
PubMed1988

Alpha-1- and alpha-2-noradrenergic receptors modulate lordosis behavior in female guinea pigs.

Modulation of lordosis behavior by stimulation of noradrenergic receptor subtypes was examined in ovariectomized, estradiol benzoate (10 micrograms)-primed guinea pigs. In the first experiment, subcutaneous administration of the alpha-2-noradrenergic agonist, UK-14,304 (0.01, 0.5, or 1.0 mg/kg, Pfizer Central Research), produced a significant increase in lordosis behavior when these animals were compared with estrogen-primed control animals injected with saline. In a second experiment, estrogen-primed animals were injected with the alpha-1-noradrenergic agonist methoxamine (0.5 mg/kg, s.c.), UK-14,304 (0.5 mg/kg, s.c.), or both drugs given together. Methoxamine or UK-14,304 administered alone facilitated lordosis in fewer than 50% of animals (17 and 39%, respectively). However, when both drugs were given together, 76% of the animals became sexually receptive. A third experiment showed that lordosis behavior facilitated by UK-14,304 could be attenuated by the administration of the alpha-2-noradrenergic antagonist idazoxan (2.5 mg/kg, s.c.). Only 29% of sexually receptive animals (i.e. those animals primed with estradiol benzoate plus UK-14,304) continued to show lordosis after they received idazoxan. The results obtained from these and previously reported experiments suggest that both alpha-1- and alpha-2-noradrenergic receptors are involved in the regulation of lordosis behavior in the guinea pig.

Animals↗
PubMed1987

Cytosol androgen receptors in guinea pig brain and pituitary.

Cytosol androgen receptors were assayed in guinea pig brain and pituitary tissues, using [3H]R1881 as ligand. These receptors had an apparent Kd of 0.04 nM and were androgen-specific (R1881 greater than dihydrotestosterone greater than testosterone = estradiol greater than progesterone). Concentrations of cytosol androgen receptors in castrated adult male guinea pigs were 12.2, 11.6, 6.9, 2.6 and 1.3 fmol per mg protein in anterior pituitary, hypothalamus, medial preoptic area, amygdala and cortex, respectively. No significant differences in receptor levels were observed between castrated adult males and females. The concentration of androgen receptors was significantly lower in the hypothalamus, medial preoptic area and anterior pituitary of castrated neonatal males than in castrated adult male guinea pigs. The systemic injection of the alpha 1-adrenergic antagonist, prazosin, had no significant influence on androgen receptor levels in castrated males in any brain area.

Age Factors↗
PubMed1987

Noradrenergic regulation of alpha 1-receptors during the postnatal development of the guinea pig.

In guinea pig brain, alpha 1-noradrenergic receptor concentrations undergo region-specific fluctuations during the first weeks of postnatal life. However, the factors involved in the regulation of these receptors have yet to be identified. In this study, the ontogeny of one possible regulatory factor, norepinephrine, was examined in relation to postnatal changes in alpha 1-receptor levels in several different regions of guinea pig brain. Results from these studies showed that while the activity of the noradrenergic system increased throughout the first weeks of postnatal development in each brain area examined, the concentration of alpha 1-receptors decreased in preoptic area and hypothalamus and increased in cortex. In subsequent experiments, the effects of noradrenergic lesions with 6-hydroxydopamine on alpha 1-receptor levels were assessed to examine the possibility that alpha 1-receptors are differentially sensitive to noradrenergic stimulation in cortex and preoptic area/hypothalamus in immature guinea pigs. Noradrenergic lesions which reduced norepinephrine levels by 87-94% resulted in significant elevations in alpha 1-receptors in all regions examined. These results are discussed with reference to the anatomical distribution of alpha 1-receptors and their regulation by norepinephrine.

Animals↗
PubMed1987

Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs.

These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior.

Adrenergic alpha-Antagonists↗
PubMed1986

Noradrenergic modulation of hypothalamic progestin receptors in female guinea pigs is specific to the ventromedial nucleus.

The concentration of estrogen-induced cytosolic progestin receptors (CPRs) in the hypothalamus of alpha 1-noradrenergic antagonist-treated female guinea pigs is reduced relative to non-drug-treated controls. The present study determined where within the hypothalamus this reduction occurs. Ovariectomized, estradiol-treated guinea pigs were given either the alpha 1-noradrenergic antagonist prazosin or vehicle. Microdissected brain regions were assayed for CPR levels. Prazosin caused a selective relative decrease in CPR levels of the ventromedial nucleus of the hypothalamus. No significant effects of prazosin were seen in other hypothalamic or preoptic area nuclei.

Animals↗
PubMed1986

Estrogen induction of progestin receptors in microdissected hypothalamic and limbic nuclei of female guinea pigs.

Estrogen induction of cytosolic progestin receptors (CPRs) in the hypothalamus-preoptic area of the female guinea pig is correlated with facilitation of female sexual behavior and gonadotropin secretion by progesterone. The present study validated a CPR microassay and determined where, within microdissected areas of the hypothalamus-preoptic area of the female guinea pig, induction of CPRs by estradiol occurs. Ovariectomized adult guinea pigs were given 20 micrograms estradiol benzoate (EB) or oil vehicle for 3 successive days. CPRs were measured using the synthetic progestin [3H]-R5020. The highest basal (no estrogen treatment) level of CPRs was seen in the arcuate-median eminence (34.1 +/- 3.7 fmol/mg). With EB treatment, the highest level of CPRs was again in the arcuate-median eminence (178.0 +/- 12.0 fmol/mg). EB-treated females also had high CPR levels in the periventricular area (88.5 +/- 10.8 fmol/mg) and the medial preoptic area (86.3 +/- 9.3 fmol/mg). Moderate levels were seen in the ventromedial nucleus of the hypothalamus (32.7 +/- 3.0 fmol/mg) and in the anterior hypothalamic nucleus (13.0 +/- 2.1 fmol/mg), but these were not significantly different from the low levels in the medial amygdala (4.5 +/- 1.2 fmol/mg) and in the dorsomedial nucleus of the hypothalamus (5.4 +/- 1.1 fmol/mg) of EB-treated females. However, EB caused a significant induction over baseline levels not only in the arcuate-median eminence, periventricular area, and medial preoptic area, but also in the ventromedial nucleus of the hypothalamus and the anterior hypothalamic nucleus. EB did not increase CPRs in the medial amygdala or the dorsomedial nucleus of the hypothalamus.

Animals↗
PubMed1985

Distribution of cholinergic muscarinic binding sites in guinea-pig brain as determined by in vitro autoradiography of [3H]N-methyl scopolamine binding.

The distribution of muscarinic binding sites was analyzed in regions of the guinea-pig brain with semi-quantitative densitometry of [3H]N-methyl scopolamine binding, a muscarinic antagonist. In the rostral forebrain, high levels of binding were detected in the caudate putamen, nucleus accumbens and olfactory tubercle while intermediate levels of binding were observed in the medial and lateral septum, bed nucleus, and vertical and horizontal limbs of the diagonal band. The hypothalamus displayed binding that ranged from low levels in the preoptic area to intermediate levels in the mammillary nucleus. In limbic areas such as the thalamus, amygdala and hippocampus, a heterogeneous pattern of binding was evident in various subregions which tended to correspond with known innervation by cholinergic afferents. In the midbrain, binding was high in the superficial layer of the superior colliculus and the medial geniculate while intermediate binding was recorded in the lateral geniculate and the lateral aspect of the central gray. The pattern of muscarinic binding observed in the brain of the guinea-pig is similar to distributions of this binding site previously reported in the rat brain and the human brain.

Animals↗
PubMed1985

A diurnal fluctuation in medial basal hypothalamic-preoptic area cytosol estrogen receptors in ovariectomized hamsters.

Cytosol estrogen receptors (CER) were measured in ovariectomized hamsters, kept in a light:dark schedule of 14:10. Significant diurnal fluctuations in CER occurred in medial basal hypothalamus-preoptic area, but not in amygdala, anterior pituitary or uterus. Highest levels of CER in medial basal hypothalamus-preoptic area occurred 2 h before lights went out, and lowest levels 1 h after lights went out.

Animals↗
PubMed1985

Tritium-sensitive film autoradiography of guinea pig brain alpha 2-noradrenergic receptors.

Tritium-sensitive film autoradiography was used to determine the distribution of alpha2-noradrenergic receptors (i.e. [3H]p-aminoclonidine binding sites) in guinea pig forebrain. Alpha 2-Receptors are heterogeneously distributed throughout the forebrain. Many limbic system structures, such as bed nucleus of stria terminalis, medial preoptic area, medial amygdaloid nucleus and lacunosum molecular layer in hippocampus were heavily labeled. We did not quantify receptor density in areas containing principally white matter but the optical density in those areas was similar to film background suggesting a very low receptor density. Low receptor concentrations were also found in areas that do not contain a high percentage of white matter, such as lateral septum and ventromedial hypothalamic nucleus.

Animals↗
PubMed1985

Estradiol modulation of alpha 2-noradrenergic receptors in guinea pig brain assessed by tritium-sensitive film autoradiography.

In this experiment, we examined the influence of estradiol on alpha 2-noradrenergic receptor binding in the female guinea pig brain with tritium-sensitive film autoradiography. Treatment of ovariectomized guinea pigs with estradiol increased alpha 2-receptor binding in regions of the preoptic area and decreased binding in the ventromedial nucleus of the hypothalamus. There was no effect of estradiol on alpha 2-receptor concentrations in other estradiol concentrating regions or in brain areas which do not concentrate estradiol.

Animals↗