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L C Krey

Publications and source records attributed to L C Krey.

At least 55 records · Page 3Linked to original sources
PubMed1984

Do vasopressin-related peptides induce hippocampal corticosterone receptors? Implications for aging.

The aged rat shows a decline in hippocampal corticosterone receptors and dysfunction in learning and adrenocortical physiology previously linked to glucocorticoid effects upon the hippocampus. The Brattleboro rat, congenitally lacking vasopressin, also has a low number of hippocampal glucocorticoid receptors, as well as learning and endocrine impairments similar to those seen in the aged. Centrally acting vasopressin analogues correct the receptor loss in the hippocampus in the Brattleboro rat but do not influence the hippocampal receptor deficit in the aged rat. Quantitative and high resolution autoradiographic procedures were utilized to characterize the glucocorticoid receptor deficit in the aged and Brattleboro rats. Quantitative autoradiography showed that in both aged and Brattleboro subjects, losses in receptors were most extreme in the pyramidal layer of the CA3a region. High resolution autoradiography revealed striking differences in the cellular basis of the receptor losses. Brattleboro rats had decreased binding of [3H]corticosterone per neuron, whereas aged subjects, in addition, had significant losses in the number of corticosterone-concentrating neurons. Taken together, our findings indicate that the glucocorticoid receptor deficit in the Brattleboro rat probably represents a vasopressin-influenced defect in the synthesis or degradation of the receptor, whereas in the aged rat the deficit originates from loss of both receptor per neuron and the steroid-concentrating neurons themselves, and thus is most likely a permanent and pharmacologically insensitive deficit.

Aging↗
PubMed1983

Corticosterone receptors decline in a site-specific manner in the aged rat brain.

Putative glucocorticoid receptors were measured in the brain and pituitary glands of young and aged rats in vivo and in vitro. Adrenalectomized rats were injected with a set dose of radiolabeled corticosterone plus unlabeled corticosterone; 2 h later [3H]corticosterone levels were measured in purified nuclear pellets from pituitary and 5 brain regions. Substantial decreases were seen in aged subjects in the maximal number of corticosterone binding sites in hippocampus and amygdala; all other regions showed no age-related changes. In contrast, there were no declines in the nuclear uptake of [3H]dexamethasone (DEX) in the aged rat brains. Since DEX interacts selectively with non-neuronal receptors in vivo, the deficit in glucocorticoid binding is selective for neurons. Subsequent studies assessing glucocorticoid receptor levels in cytosol preparations in vitro revealed significant declines in hippocampus and amygdala quantitatively comparable to the decline observed in nuclear binding in these loci. This suggests that the primary deficit leading to nuclear depletion may be the reduction of cytosolic receptor number, rather than other possible factors such as the reduction in receptor affinity or translocation of steroid-receptor complex. This decline may play a role in a number of limbic functions which are influenced by glucocorticoids and show deficits with age.

Aging↗
PubMed1983

Aromatization: important for testosterone's developmental influences on the neurocircuits mediating cervically stimulated prolactin secretion in the female rat.

Adult female rats treated neonatally with testosterone or estrogen fail to respond to cervical stimulation with episodic prolactin release. The developmental action of testosterone is inhibited by co-administration of 1,4,6-androstatriene-3,17-dione at a dose sufficient to inhibit the testosterone-induced rise in estrogen receptors in limbic brain cell nuclei. These data suggest the importance of aromatization for testosterone action.

Animals↗
PubMed1983

Gonadal steroid modulation of LH secretion stimulated by LHRH, Ca2+ and cAMP.

Primary cultures of enzymatically dispersed rat pituitary cells were used to examine steroid effects on LH secretion stimulated by LHRH, Ca2+ and cAMP. Cultures were pretreated for 48 h with testosterone (T) or 17 beta-estradiol (E) and then challenged for 4 h with various secretogogues. T did not affect basal LH secretion; it inhibited the responses to Ca2+ and LHRH; and it potentiated the response to cAMP. E stimulated both basal LH secretion and the responses to all secretogogues, without affecting cell LH content. Thus, T affects stimulus-secretion coupling, while E affects secretion per se. All steroid effects were blocked by steroid antagonists, indicating that steroid action is receptor-mediated regardless of the secretogogue involved. The similarity of steroid effects on the responses to LHRH and Ca2+ but not cAMP suggests that Ca2+ rather than cAMP is a second messenger for LHRH, and that steroid action occurs at some step subsequent to LHRH-stimulated Ca2+ mobilization.

Animals↗
PubMed1983

The adrenocortical stress-response in the aged male rat: impairment of recovery from stress.

To test if the adrenocortical axis of the rat loses sensitivity to negative feedback control during aging, we examined corticosterone secretion under basal, stressed and post-stress conditions in young and in aged Fisher male rats. We find no age-related change in the speed or magnitude of the stress response or in the capacity to manifest a corticosterone response following chronic stress. However, we do observe in aging rats an elevation of basal corticosterone and an impaired capacity to adapt to and recover from stress. This latter finding is illustrated by longer latencies relative to young rats, in the return of serum corticosterone concentrations to basal values during sustained exposure to mild cold or following the end of immobilization stress. All of these deficits reflect an increased rate of corticosterone secretion during physiologically inappropriate circumstances. Such observations support the concept that there is an age-related loss of sensitivity of the brain and pituitary to the inhibitory effects of high circulating levels of corticosterone on ACTH release.

Adaptation, Physiological↗
PubMed1983

Behavioral and neuroendocrine effects of long-term progesterone treatment in the rat.

Progesterone and estradiol, alone or in combination, were administered to ovariectomized rats for 2 weeks. Progesterone alone had no effect on body weight, luteinizing hormone (LH) secretion, receptivity or brain cytoplasmic progestin receptors (CPR). Progesterone in combination with estradiol significantly attenuated estrogen suppression of weight gain and estrogen stimulation of receptivity, the LH afternoon surge and induction of CPR, but did not affect the negative feedback of estrogen on morning LH levels. The decrease in CPR after 2 weeks of progesterone is very similar in magnitude to the decrease observed following acute treatment, suggesting that, unlike neurotransmitter agonists and glucocorticoids, progesterone does not cause down regulation of its receptors in the brain following chronic treatment.

Animals↗
PubMed1982

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Amygdala↗
PubMed1982

Gonadal steroid modulation of LHRH-stimulated LH secretion by pituitary cell cultures.

Enzymatically dispersed rat pituitary cells were grown in primary culture, and LHRH-stimulated LH secretion was measured. Testosterone (T) decreased and 17 beta-estradiol (E) increased pituitary responsiveness to LHRH. The effect of E on LH secretion was partly due to an increase in LH content. There was a latent period of 12 h for E and 18 h for T between the onset of steroid treatment and the manifestation of steroid action. Neither steroid was required to be continuously present in order to exert its effects. After steroid withdrawal, the effect of T persisted for 72 h and that of E for more than 96 h. The actions of both steroids were blocked by protein-synthesis inhibitors. These results are consistent with the hypothesis that steroid effects rely on a mechanism involving alterations in protein synthesis; the affected proteins may be involved in the process of LHRH action.

Animals↗
PubMed1982

Characterization of estrogen stimuli sufficient to initiate cyclic luteinizing hormone release in acutely ovariectomized rats.

Estradiol (E)-filled Silastic capsules were implanted subcutaneously to characterize the estrogen stimulus sufficient to initiate cyclic LH secretion in female rats ovariectomized on diestrus 1 of the estrous cycle. Such capsules elevate preoptic area, hypothalamic and hypophysial cell nuclear estrogen receptor levels to proestrous values within 1/2 h following insertion; upon removal of the capsules, nuclear receptor levels decline monotonically to ovariectomized control levels by 8 h in brain and 12 h in pituitary. Three parameters of the E stimulus were studied: latent period, duration, and continuity. E stimuli, short in duration (7-12 h) and discontinuous in nature (3 h pulses 12 or 15 h apart), effectively stimulated LH surges on "proestrus'. However, these stimuli had to begin 30 h prior to the onset of LH release. Such a latent period for estrogen action was not observed when we monitored the ability of the same E stimuli to enhance pituitary responsiveness to GnRH. These studies demonstrate that the "rate-limiting step' for estrogen's positive feedback action is located within the estrogen-sensitive brain circuits controlling GnRH release and defines the temporal characteristics of E stimuli activating these circuits.

Animals↗
PubMed1981

The luteinizing hormone releasing hormone (LHRH) neuronal networks of the guinea pig brain. III. The regulation of cyclic gonadotropin secretion.

The effects of selected CNS lesions on the ovulatory cycle as well as the distribution of LHRH terminals in the median eminence of the female guinea pig were examined. Radiofrequency lesions were placed in the medial preoptic area (MPOA) or suprachiasmatic nucleus (SCN). Animals were studied for varying lengths of time (1-5 months) following lesion placement. The occurrence of at least two ovulatory cycles was determined by cyclicity in vaginal opening, the presence of viable corpora lutea and measurements of luteal phase elevations in serum progesterone. The distribution of LHRH immunoreactivity was determined by immunocytochemical procedures on Bouin's fixed, paraffin-embedded brain sections. Lesions of the MPOA or SCN resulted in different degrees of loss of LHRH fibers in the zona externa of the ventral and lateral aspects of the infundibular stalk as well as complete loss of terminals throughout the zona interna. Despite depletion of LHRH fibers, all animals with SCN (n = 8) and the majority with MPOA (4/6) lesions showed regular ovulatory cycles. Two females with MPOA lesions presented two different anovulatory syndromes. Anovulation appeared unrelated to the size or site of the lesions or in the degree of depletion of LHRH fibers in the infundibulum. It would appear that these brain areas and their LHRH projections are not essential for cyclic gonadotropic release.

Animals↗
PubMed1981

Temporal relationship between cell nuclear progestin receptor levels and sexual receptivity following intravenous progesterone administration.

This study was designed to assess the temporal relationship between the appearance and retention of cell nuclear progestin receptors in hypothalamus and the facilitation and decline of feminine sexual behavior following an i.v. injection of progesterone (P). Nuclear translocation of progestin receptors preceded the earliest appearance of behavior. The behavioral effects of P outlasted the nuclear progestin receptor elevation by several hours. Our results are consistent with the idea that P-induced effects on feminine sexual behavior involve genomic activation.

Animals↗
PubMed1981

Danazol suppression of luteinizing hormone secretion: a role for danazol-androgen receptor interaction within the brain-pituitary complex.

We investigated the relationship between intracellular androgen and estrogen receptors within the brain-pituitary complex and danazol suppression of luteinizing hormone secretion in castrated rats. Danazol did not influence 3H-estradiol-estrogen receptor interactions within the brain and pituitary but did suppress 3H-dihydrotestosterone-androgen receptor interactions within this neuroendocrine complex. To study the significance of these danazol-androgen receptor interactions, the drug was administered to androgen receptor-deficient pseudohermaphrodite or flutamide-treated male rats. In both instances, danazol suppression of luteinizing hormone release was markedly attenuated or absent. These findings point to danazol-androgen receptor interactions within the brain-pituitary complex as a key step in this drug's antigonadotropic actions. Whether the active drug form is danazol itself or a metabolite is subject to further study.

Amygdala↗
PubMed1981

Adrenal steroid inhibition of the vasopressin-neurophysin neurosecretory system to the median eminence of the rat. Differential effects of corticosterone and deoxycorticosterone administration after adrenalectomy.

Neurophysin and vasopressin-containing terminals in the zona externa of the median eminence (ZE) show a large increase in immunoreactive peptide following adrenalectomy which can be prevented by dexamethazone replacement therapy. The present study was undertaken to determine the effectiveness of a glucocorticoid (corticosterone; CS) and a mineralocorticoid (deoxycorticosterone: DOC) in exerting negative feedback on this system. Animals were adrenalectomized and implanted with various sized pellets of either steroid or cholesterol. The amount of neurophysin-immunoreactivity in the ZE 2 weeks after adrenalectomy was estimated on a zero to four rank scale independently by three observers. The data were analyzed by the X2 statistic. Low doses of CS (50 mg) reduced the amount of staining in comparison to cholesterol-replaced animals by approximately 50%. The ZE of animals receiving higher doses (100--200 mg) were identical to those of intact animals. DOC, however, at the 50 or 100 mg level produced only a slight inhibition of the response to adrenalectomy. Larger pellets (150--200 mg) did not result in a level of ZE staining as low as for intact animals. These findings suggest that the vasopressin neurosecretory system to the ZE is regulated by glucocorticoids.

Adrenalectomy↗