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B Nock

Publications and source records attributed to B Nock.

At least 19 recordsLinked to original sources
PubMed1992

Nitric oxide control of steroidogenesis: endocrine effects of NG-nitro-L-arginine and comparisons to alcohol.

Recent studies suggest that nitric oxide (NO) may regulate hormone biosynthesis and secretion. This was tested by treating male rats with NG-nitro-L-arginine methyl ester (NAME), a NO synthase inhibitor, and measuring serum and testicular interstitial fluid testosterone and serum corticosterone, luteinizing hormone (LH), and prolactin (PRL). The effect of NG-nitro-L-arginine (NA), a less-soluble form of the same NO synthase inhibitor, on the reproductive suppressant actions of alcohol was also examined. NAME increased testosterone and corticosterone secretion dose-dependently without affecting LH and PRL secretion. The alcohol-induced suppression of testosterone or LH secretion was not altered by treatment with NA. Although effects of NAME and NA on other systems may be involved, these results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.

Analysis of Variance↗
PubMed1992

A simple, highly sensitive assay for measurement of digitonin during receptor solubilization.

A simple and highly sensitive assay for measuring total digitonin in biological samples is described. The assay is based on the ability of digitonin to hemolyze red blood cells. The precision and reproducibility of the assay was excellent with intra- and inter-assay variabilities of less than 1% and 6%, respectively. The assay was used to evaluate several potential methods for removing digitonin from biological samples (digitonin extracts from guinea pig brain membranes). Dialysis and G-25 Sephadex chromatography were ineffective. However, protein and digitonin can be effectively separated by ammonium sulfate precipitation followed by dialysis. The kappa 1 opioid receptor survived these procedures with no change in affinity for [3H]U-69,593. In conclusion, the hemolytic assay for digitonin appears to provide a practical means for determining detergent concentrations during receptor purification and characterization and for evaluating potential methods for detergent removal. Although an in depth analysis of the assay was carried out only for digitonin, CHAPS and deoxycholate also caused 50% hemolysis at concentrations well below those commonly used for receptor solubilization and, therefore, the general assay procedures might have applicability for measurement of these and perhaps other detergents used in receptor solubilization as well.

Animals↗
PubMed1991

Morphine suppresses the ovarian steroid hormone-dependent lordosis response of female guinea pigs: reversal by naloxone but not clonidine.

The opiate agonist morphine caused a dose- and time-dependent suppression of lordosis responding in ovariectomized guinea pigs treated with estradiol-17 beta and progesterone. The suppression of lordosis by morphine appears to be mediated by opiate receptors since the opiate antagonist naloxone blocked its effects both in terms of the percentage of animals showing lordosis and the duration of individual responses. Naloxone, when given alone, did not affect lordosis responding in estradiol-17 beta + progesterone-primed animals and did not induce lordosis in animals primed with estradiol-17 beta alone. Thus, endogenous opioids might not tonically inhibit lordosis under the physiological conditions examined. The alpha-noradrenergic agonist clonidine did not reverse the effects of morphine on lordosis. Thus, the inhibitory effects of morphine on this behavior might be independent of its presynaptic effects on norepinephrine release in brain.

Animals↗
PubMed1991

Influence of morphine exposure during adolescence on the sexual maturation of male rats and the development of their offspring.

The effects of adolescent morphine exposure on the sexual maturation of male rats, their reproductive capacity and the development of their progeny were examined. Groups of prepubescent male rates (25-27 days of age) were implanted with morphine- or placebo-pellets (one on Day 1, then two pellets on Days 4, 7 and 10); the pellets were not removed to assure the sustained release of morphine for 3 to 4 weeks and to avoid the confounding effects of a precipitated withdrawal syndrome. Groups of animals were sacrificed at weekly intervals through adulthood for an assessment of reproductive endocrine function. A large group, however, was also bred with drug-naive primiparous females at 85 days of age (8 weeks after morphine or placebo pellet implantation), when the acute and chronic effects of morphine on reproductive endocrine parameters had dissipated; their fertility and the development of the male and female progeny was characterized. Our results indicated that morphine exposure during adolescence led to a pronounced inhibition of a number of indices of sexual maturation (e.g., serum testosterone and luteinizing hormone levels and reduced weights of the testes and seminal vesicles). Breeding morphine- and placebo-implanted male rats with drug-naive females resulted in smaller liters derived from morphine-treated fathers when compared to controls, but in all other respects the development of the offspring in the two groups were equivalent. However, upon reaching adulthood, a number of selective endocrine differences were detected in morphine-derived offspring when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Muscarinic cholinergic receptors in the songbird and quail brain: a quantitative autoradiographic study.

In order to clarify the neuroanatomical basis for postulated muscarinic cholinergic control of a wide array of physiological processes in birds, the distribution of muscarinic cholinergic receptors in the brain of three avian species was investigated by quantitative autoradiography. The species consisted of two passerines (songbirds), the European starling (Sturnus vulgaris) and the song sparrow (Melospiza melodia), and one galliform, the Japanese quail (Coturnix coturnix japonica). [3H]N-methyl scopolamine (NMS), a muscarinic cholinergic antagonist was used as the ligand to label the receptors. Initial experiments demonstrated that the binding of this ligand in the three species is saturable in the nanomolar range and has a high affinity (Kd = +/- 0.6 nM). Displacement experiments revealed that three muscarinic ligands competed in an order of potency characteristic of the mammalian muscarinic receptor (i.e., atropine greater than oxotremorine greater than carbachol) for NMS binding in the avian brain. In all three species, portions of the basal ganglia, such as the parolfactory lobe and the paleostriatum augmentatum, exhibited the highest density of binding. On the other hand, the paleostriatum primitivum, the avian homologue of the mammalian globus pallidus, contained very few binding sites. Other telencephalic sites, such as the ventral and dorsal hyperstriatum, also revealed relatively high receptor density. However, the neostriatum and especially the ectostriatum showed much lower levels. In the hypothalamus, in all three species, specific binding could be observed in the ventromedial nucleus and adjacent areas. The paraventricular nucleus also showed moderate levels of binding density, especially in the two songbird taxa. At a more rostral level, the preoptic area showed low levels of binding. In the quail, the sexually dimorphic nucleus of the preoptic area was clearly outlined in the autoradiograms by the low level of binding sites compared to the surrounding areas. In the two passerine species, nuclei of the song system were identified by either high or low levels of NMS binding. High binding defined area X and the mesencephalic nucleus, intercollicularis (ICo). In contrast, the robust nucleus of the archistriatum and the magnocellular nucleus of the anterior neostriatum showed low levels of binding in comparison with the surrounding tissue. None of these nuclei were visible in the quail autoradiograms except for ICo, which appeared as in the passerines as a heavily labelled area surrounding the lightly labelled nucleus mesencephalicus lateralis pars dorsalis. In all three species, the hippocampal complex was devoid of NMS binding except for two lateral dark bands that were present along the entire rostral to caudal extent of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Affinity of drugs and peptides for U-69,593-sensitive and -insensitive kappa opiate binding sites: the U-69,593-insensitive site appears to be the beta endorphin-specific epsilon receptor.

In vitro competition studies with rat brain were performed to systematically define the characteristics of the [3H]U-69,593 binding site and of the site selectively labeled by [3H]EKC (in the presence of U-69,593 and mu and delta blocking agents). The [3H]U-69,593 site has a binding selectivity profile that corresponds to that of the kappa opiate receptor. That is, all kappa compounds, regardless of chemical class, and dynorphin A, the putative endogenous ligand for kappa receptors, bind to the site with high affinities, whereas mu and delta ligands and nonopiate compounds do not. The agonists U-69,593, ICI 197,067 and U-50,488 and antagonist nor-binaltorphimine were found to have a useful degree of selectivity for the site. The [3H]EKC site has opiate receptor characteristics and appears to be the most abundant opiate receptor in rat brain, but its binding selectivity profile is not that of a kappa receptor. Instead, this non-mu, non-delta, non-kappa site has the pharmacological properties that correspond to those of the beta-endorphin-specific, epsilon receptor that has been hypothesized to exist for some time. We could not identify any compound that is selective for the putative epsilon site. Of the more than 50 compounds tested, all were either equally potent at the [3H]U-69,593 and [3H]EKC sites or were more potent at the [3H]U-69,593 site.

Analgesics↗
PubMed1990

Antagonist-induced up-regulation of the putative epsilon opioid receptor in rat brain: comparison with kappa, mu and delta opioid receptors.

We reported previously that in the presence of appropriate blocking agents [3H]ethylketocyclazocine selectively labels a non-mu, non-delta, non-kappa binding site with opioid receptor characteristics. We now report that chronic treatment with the opiate antagonist naltrexone dramatically increases the number of these binding sites in rat brain, as well as the number of mu, delta and kappa receptors. This finding further supports the concept that the [3H]ethylketocyclazocine site is an opioid receptor and previously reported evidence indicating that it might be the beta-endorphin-specific epsilon receptor that has been hypothesized to exist for some time. The affinity of naltrexone for the putative epsilon site in vivo appears to be similar to its affinity for mu and delta receptors, since a single 30-mg naltrexone pellet was sufficient to induce a maximal rate of up-regulation for all three types of sites. In contrast, a maximal rate of kappa receptor up-regulation requires at least four naltrexone pellets and, therefore, the affinity of naltrexone for this site in vivo appears to be considerably lower than for the other sites. Unexpectedly, we found that the naltrexone-induced increase in binding to all four types of receptors continued to increase through 60 days of naltrexone exposure, the longest treatment period examined, and that the increases in receptor binding were linear with exposure time. This finding is contradictory to the generally held view that antagonist-induced opioid receptor up-regulation in brain increases asymptotically, leveling off after a relatively brief treatment period.

Animals↗
PubMed1990

Influence of chronic alcohol administration on representative indices of puberty and sexual maturation in male rats and the development of their progeny.

The effects of chronic alcohol administration on reproductive endocrinology in the developing male rat were examined. Prepubescent male rats (25 days of age) were maintained on an alcohol liquid diet or were pair-fed a control diet until early adulthood and selected indices of sexual maturation were examined at weekly intervals. To determine whether sexually immature animals were more sensitive to the effects of alcohol than adults, fully mature male animals were exposed to an identical period of alcohol exposure and comparisons were made between the two groups. The results demonstrated that alcohol significantly affected many of the primary indices of puberty and sexual maturation. The normal pubertal increases in serum testosterone levels, the weights of the testes and secondary sex organs and beta-endorphin levels in the hypothalamus were substantially reduced in alcohol-exposed animals compared with controls. In contrast to these results, the effects of alcohol on reproductive endocrinology in the fully mature animal were transitory and of considerably less magnitude. After a 2-week alcohol-free period, male rats exposed to alcohol during development were bred with drug-naive primiparous females. Although the same number of pregnancies resulted from matings between alcohol-exposed males and drug-naive females compared with controls, litter sizes were significantly smaller in alcohol-derived offspring than in controls. In all other respects, such as body weights, sex ratios, mortality rates and gross developmental features (eye opening, incisor eruption and testes descent), alcohol-derived offspring were identical with controls. Upon closer examination, however, significant disturbances were detected in alcohol-derived male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Castration-induced changes in the response of the hypothalamic-pituitary axis to alcohol in the male rat.

In an attempt to determine the direct effects of alcohol on the hypothalamic-pituitary aspect of the hypothalamic-pituitary-gonadal axis, we examined the effects of alcohol on serum luteinizing hormone (LH) levels in the normal and testosterone-depleted castrated male rat. We found that within several days after castration (2-4 days) alcohol, at low to moderate doses, was only modestly effective in suppressing serum LH levels, whereas in sham-operated controls it was maximally effective at all doses tested. Surprisingly, at very high doses (4-6 g/kg), alcohol not only did not depress serum LH levels in long-term castrated rats, but elevated them by 2- to 4-fold when compared to saline-injected controls. The loss of sensitivity of the hypothalamic-pituitary axis to alcohol observed in castrated rats appeared to be selective, inasmuch as the mortality rate at high doses of alcohol was significantly (P less than .01) greater in castrated rats, when compared to sham-operated controls, and other measures of central nervous system impairment were equivalent in both groups. At the present time, it is difficult to explain this biphasic effect of alcohol on serum LH in the castrated animal, but our results are consistent with the hypothesis that the effects of alcohol on gonadotropin release may be dependent to a significant degree on the steroid milieu at the time of the experiments.

Aldehyde Dehydrogenase↗
PubMed1989

Sex differences in cytosolic progestin receptors in microdissected regions of the hypothalamus/preoptic area of guinea pigs.

Cytosolic progestin receptors (CPRs) were measured in microdissected nuclei of the hypothalamus and preoptic area of male and female guinea pigs. Adult gonadectomized animals were given 3 daily injections of 20 micrograms/day estradiol benzoate (EB) or oil vehicle. 24 h later, animals were sacrificed and cytosolic progestin receptors were measured using the synthetic progestin 3H-R5020. CPR levels did not differ significantly between oil treated males and oil treated females in any brain areas examined. With EB treatment, males showed significant increases in CPRs in most of the brain areas in which females showed increases, i.e. in the medial preoptic area, the periventricular part of the preoptic area, the periventricular part of the anterior hypothalamus, the ventromedial nucleus of the hypothalamus, the periventricular part of the medial hypothalamus and the arcuate-median eminence. However, EB treated males showed significantly lower CPR levels than EB treated females in both the periventricular part of the preoptic area and the periventricular part of the medial hypothalamus.

Animals↗
PubMed1989

Photoperiodic changes in opiate binding and their functional implications in golden hamsters.

Daylength modulates gonadotropin secretion, gonadal steroid hormone feedback, sexual behavior and body weight in male golden hamsters. Endogenous opiates regulate each of these phenomena, and the ability of opiate receptor blockade to elevate serum LH secretion is photoperiod-dependent. We used in vitro autoradiography to localize and quantify effects of daylength in golden hamsters. Hamsters were exposed to stimulatory (14 h light: 10 h dark) or inhibitory (10 h light: 14 h dark) photoperiods for 10 weeks before specific [3H]naloxone binding was assessed. Short days significantly decreased binding in medial amygdala and the intercalated amygdaloid nucleus. This effect was reversed by superior cervical ganglionectomy. No significant effects of daylength were observed in other amygdaloid, hypothalamic or preoptic areas. Lesions of the medial amygdala decreased copulatory behavior, short day-induced weight loss, and anogenital chemoinvestigation but did not affect gonadal regression or other forms of chemoinvestigation. These lesions facilitated testosterone's negative feedback on luteinizing hormone in long days but did not interfere with the potentiation of negative feedback by short days.

Animals↗
PubMed1989

Distribution of alpha 2-adrenergic receptors in the brain of the Japanese quail as determined by quantitative autoradiography: implications for the control of sexually dimorphic reproductive processes.

With the use of [3H]p-aminoclonidine (PAC), alpha 2-adrenergic binding sites were mapped in the brain of the Japanese quail (Coturnix coturnix japonica). The sites were labeled with the use of in vitro quantitative autoradiography. Special attention was given to areas implicated in the control of sexually dimorphic reproductive processes including sexual behavior. Preliminary competition experiments found that [3H]PAC binding on tissue sections exhibited a pharmacology appropriate to the alpha 2 receptor. Binding sites were found to be heterogeneously distributed throughout the brain. Some of the highest levels of specific binding were found in several areas regulating reproductive function such as the preoptic area, the supraoptic nucleus, the infundibulum, and the medial mammillary nucleus of the infundibulum. [3H]PAC labeled precisely the morphologically dimorphic preoptic medial nucleus but no sexual dimorphism in density of receptor binding was identified. However, dimorphism in density of receptor binding was identified in two areas: the medial mammillary nucleus and the mesencephalic intercollicular nucleus. The former area appears to be involved in the regulation of gonadotrophin secretion and the latter area has been implicated in the control of vocal behavior. These neurochemical dimorphisms may contribute to the regulation of two sexually dimorphic reproductive processes, gonadotropin secretion and courtship vocalizations.

Adrenergic alpha-Agonists↗
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

In vivo evidence for a direct effect of naloxone on testicular steroidogenesis in the male rat.

It has been suggested that endogenous opioid peptides (EOP) exert paracrine or autocrine effects in the testes. To assess this hypothesis, we examined whether naloxone, by blocking the effects of EOP, influenced serum testosterone levels, apart from its effects on LHRH/LH, in the intact male rat. We found that naloxone increased serum LH and testosterone levels over essentially the same time course and produced dose-dependent increases in serum testosterone levels even though LH levels were maximally elevated at all doses. These data are not consistent with the view that naloxone exerts its effects on testosterone exclusively by altering LHRH/LH release. Additional, perhaps more definitive, evidence of a direct effect of naloxone on testosterone's biosynthesis was provided by our observations that 1) naloxone generated increases in serum testosterone levels in male rats in which the naloxone-induced surge in LH was blocked by nembutal; and 2) intratesticular injections of naloxone increased serum testosterone levels without increasing LH. Although these data suggest that naloxone influences steroidogenesis independently of its effects on LH, we found that the antagonist failed to increase serum testosterone levels in hypophysectomized animals or when serum LH levels were allowed to reach undetectable levels in nembutal-blocked animals. Consequently, our data are consistent with the hypothesis that naloxone facilitates the effects of LH on testosterone's biosynthesis rather than exerting an independent effect of its own. Whether the effects observed in these studies represent a negative autocrine effect of EOP on Leydig cells or a paracrine effect on Sertoli cells remains to be determined. Nevertheless, our results provide, to our knowledge, the first in vivo evidence that EOP modulate testicular steroidogenesis in the intact animal.

Animals↗
PubMed1989

Age-related differences in the sensitivity to opiate-induced perturbations in reproductive endocrinology in the developing and adult male rat.

The effects of a single morphine pellet (75 mg) implanted in developing male rats at 27 days of age on reproductive endocrine parameters were compared to those found in adult (65-day-old) animals after the same treatment. The pellets were left in place to provide the release of morphine during critical phases of puberty and sexual maturation and to prevent an abrupt withdrawal syndrome upon pellet removal which would confound our results. Developing rats were sacrificed at representative intervals after pellet insertion to assess the development of key indices of reproductive endocrinology; adult rats were sacrificed at the same time intervals to permit an evaluation of age-related differences in the sensitivity to opiate-induced endocrine disturbances. Our results showed that morphine markedly influenced a number of endocrine parameters associated with the maturation of the hypothalamic-pituitary-gonadal axis in developing rats for prolonged periods of time, whereas the effects of the opiate in the adult rat were relatively modest and transient. In the developing rat, serum luteinizing hormone (LH), testosterone, the wet tissue weights of the seminal vesicles and testes and hypothalamic LH-releasing hormone (LHRH) levels were substantially depressed immediately after pellet implantation and these effects persisted for up to 4 weeks when compared to placebo-implanted, age-matched controls. In contrast to these results, adult rats showed only transient effects (less than 1 week) of morphine on certain reproductive endocrine parameters (e.g., serum LH, testosterone and the weights of the seminal vesicles) and no effects on others (e.g., testes weights and hypothalamic LHRH).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

Autoradiography of [3H]U-69593 binding sites in rat brain: evidence for kappa opioid receptor subtypes.

In vitro quantitative autoradiography was used to determine the distribution of [3H]U-69593 binding sites in rat brain. The highest density of binding was found in areas of the tel- and diencephalon while certain areas of the mes- and metencephalon were moderately labeled. The distribution of [3H]U-69593 binding sites corresponds closely (but not precisely) to the distribution of sites labeled by [3H]EKC and [3H]bremazocine at room temperature but differs substantially from the distribution of sites labeled by [3H]EKC at 4 degrees C (as described by others). These anatomical findings support previous biochemical evidence indicating that [3H]U-69593 selectively labels a kappa opioid receptor subtype with characteristics that differ from the kappa receptors labeled by [3H]EKC at 4 degrees C.

Analgesics↗
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↗