摘要:

In the absence of universal equations expressing neurobiological findings, the safest theoretical approach for the neuroendocrinologist is to start from axiomatic requirements for biologically adaptive neural mechanisms, in our case for reproduction. From this emerge two themes: the likely importance of interactions between internal (hormonal) and external signals in controlling gene expression relevant to reproductive functions; and, second, the vision of molecular interactions on DNA subserving environmental impacts on reproduction. The first theoretical notion has so far yielded data showing a role for synaptic inputs during the onset of estradiol actions for the hormone's induction of enkephalin mRNA, a finding which parallels earlier behavioral results. As well, noxious somatosensory inputs interact with estrogens and progesterone in their influence on enkephalin gene expression. The second theme led to novel investigations of thyroid influences on reproductive molecular biology and behavior, including the ability of exogenous or endogenous thyroid hormones to reduce female mating responses. Since elevated thyroid hormone levels could signal environmental cold, our experiments offer the possibility of explaining ethological facts at a molecular level. More generally, nuclear hormone receptor interactions on the surface of DNA may offer a new level of neural integration revealed first by hormone effects in neuroendocrine cells.

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04691.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

Antidepressant drugs have in common a delayed onset of clinical efficacy. In rats, long‐term, daily administration of four different types of clinically effective antidepressant drugs results in decreased corticotropin releasing hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus (PVN). Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (Arc) projects to the PVN, we measured NPY and POMC mRNA expression in the Arc usingin situhybridization histochemistry at several time points following daily administration of four different antidepressant drugs. After 14 and 56 days of imipramine treatment, Arc NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged compared to control after one or five days of treatment. Arc POMC mRNA levels are unchanged compared to controls at 1, 5, 14, or 56 days following imipramine treatment. Unlike after imipramine, Arc NPY and POMC mRNA levels are increased significantly to 134–172% of control following 56‐day treatment with the antidepressant drugs fluoxetine, phenelzine, or idazoxan. The divergent effects of imipraminevsthe other 3 antidepressant drugs on Arc NPY mRNA expression are similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression levels in the locus coeruleus (LC) using the same experimental paradigm, but are different from the unidirectional depressive effects of all four drugs on CRH mRNA expression in the PVN. Thus, the Arc NPY and LC noradrenergic systems may act coordinately in mediating antidepressant effects. The present data are consistent with the delayed onset of clinical efficacy for antidepressant drugs, and suggest that Arc NPY and POMC neurotransmitter systems play a role in the pathophysiology of depre

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04422.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

The mating‐induced preovulatory surge of luteinizing hormone (LH) lasts for at least 12 h in the female ferret. This prolonged increase in circulating LH is presumably accompanied by a corresponding elevation in the activity and output of luteinizing hormone‐releasing hormone (LHRH) neurons projecting to the hypothalamic‐hypophyseal portal blood vessels and adenohypophysis. We used the protein products of the immediate early genes (IEGs) c‐fos, and c‐junas markers of neural activation in order to determine whether a sub‐population of LHRH neurons is differentially activated by mating and whether non‐LHRH neurons in specific forebrain regions are selectively activated at different times during the mating‐induced preovulatory LH surge. In Experiment 1, estrous female ferrets were perfused 0.5, 1.5, 3.0, 6.0 or 12.0 h after receiving one 5‐min intromission from a male or after being placed alone in a testing cage for 20 min. Fos‐like immunoreactivity (Fos‐IR; Oncogene Ab‐2 antiserum) and LHRH‐like immunoreactivity (LHRH‐IR; LR‐1 antiserum) were visualized. The percentage of Fos‐IR LHRH neurons was significantly augmented 1.5 h after mating but had returned to basal levels by 3.0 h. The double‐labeled LHRH neurons were concentrated in the caudal medio‐basal hypothalamus. In non‐LHRH neurons the number of Fos‐IR neural nuclei was significantly increased by mating in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MA), ventrolateral hypothalamus (VLH), and midbrain central tegmental field (CTF) 1.5 h after mating but, as in LHRH neurons, had returned to basal levels by 3.0 h. In Experiment 2, estrous females were perfused 1.5 h or 8.0 h after either receiving one 5‐min intromission or being placed alone in a testing cage, and the brains were processed for LHRH and c‐Fos‐like (DCH‐1, Dr Gerard Evan), c‐Jun‐like (Jun‐IR; Oncogene Ab‐2) or Egr‐1‐like (Egr‐IR; Santa Cruz) immunoreactivity. The percentage of LHRH neurons colabeled with both Fos‐IR and Jun‐IR was significantly greater in the 1.5 h group than in the unpaired group. Again, the induction of these IEG products occurred in LHRH neurons in the caudal medio‐basal hypothalamus. Mating significantly increased the number of Fos‐IR non‐LHRH neural nuclei in the MPOA, BNST, MA, VMH and CTF, as well as the number of Egr‐IR nuclei in the MPOA, BNST and MA in the 1.5 h group. By contrast, the number of Jun‐IR non‐LHRH neurons was unaffected by mating. In these Experiments we have identified a sub‐population of LHRH neurons which, using Fos and Jun as markers of neural activation, is activated by mating and may be differentially involved in the generation of the preovulatory LH surge. Although the LHRH system is presumably activated throughout the duration of the 12 h preovulatory LH surge, c‐Fos and c‐Jun immunoreactivity in LHRH neurons is augmented only transiently. Fos‐IR and Egr‐IR in non‐LHRH neurons show a similar time‐course. Together, these results suggest that the presence of augme

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04623.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

The neurochemical and behavioural effects of a novel stereotaxic surgical method developed for interrupting the nerve fibres running through the rat pituitary stalk to the posterior pituitary gland was studied. The cerebrospinal fluid (CSF) vasopressin (AVP) and oxytocin (OT) content as well as changes in aggressiveness were measured in rats one week and one month after the surgical intervention. The main results are as follows: (1) the compression of the pituitary stalk elicits a chronic increase in water consumption, as well as in CSF vasopressin and oxytocin content; (2) the surgical intervention increased the frequency of clinch fighting after one week. The increase in aggressiveness accentuated after one month and, in addition, operated animals showed reduced scores of resting while exploratory and social behaviours increased; (3) there was a strong positive correlation between water consumption, vasopressin, and aggressiveness; (4) oxytocin changes showed a positive correlation with variation in social behaviour. The surgical intervention may serve as a model for lesions of the pituitary stalk and formation of ectopic neurohypophyses in humans.

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04654.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

Pituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are hypothalamic factors that play roles in the regulation of anterior pituitary cell activity. PACAP exists in 2 forms physiologically, a 38 amino acid form (PACAP38) and a form possessing the N‐terminal 27 amino acids of PACAP38 (PACAP27). We have previously shown that PACAP38 stimulates an increase in [Ca2+]iin rat gonadotrophs. In an attempt to identify the PACAP receptor type underlying this effect, we compared the potency of PACAP38, PACAP27 and VIP to stimulate Ca2+changes in identified single rat gonadotrophs. All 3 peptides at 100 nM were capable of stimulating high amplitude Ca2+oscillations, which were also observed in the absence of extracellular Ca2+. The order of potency of these peptides was PACAP38>PACAP27>VIP, and a potent antagonist of the PACAP/VIP type II binding site ([4‐Cl‐D‐Phe6, Leu17]‐VIP) failed to block these responses, suggesting that these effects are mediated through a PACAP/VIP type 1 receptor (PVR1). The Ca2+responses to PACAP38 and VIP were unaffected by overnight treatment of the cells with pertussis toxin (PTX; 250 ng/ml) indicating that these responses are mediated by a PTX‐insensitive G‐protein. Finally, the Ca2+responses stimulated by PACAP38 and VIP were blocked by the phospholipase C‐βblocker U73122 (5 μM). In summary, PACAP stimulates Ca2+oscillations in rat gonadotrophs through the activation of the PVR1 linked to a PTX‐insensitive G‐protein and the activation of phospholipase C‐β. VIP can stimulate the same pathway in rat gonadotrophs, although it is at least 1

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04645.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

Attention has recently been focused on lactation‐induced modifications of activity of neuronal populations in the arcuate nucleus (ARC) of the mediobasal hypothalamus.The ARC hosts the tubero‐infundibular dopaminergic (TIDA system) responsible for the neuroendocrine control of prolactin (PRL), and other non‐neuroendocrine neuronal populations, such as neuropeptide Y (NPY)‐ and proopiomelanocortin (POMC)‐containing systems that are important modulators of hypothalamic gonadoliberin (GnRH) secretion. Our longstanding interest in the functional anatomy of the ARC led us to investigate whether the suckling stimulus would trigger an expression of Fos‐ir in specific arcuate neuronal populations and to possibly characterize responsive neurons by using double‐labeling immunohistochemistry. Freely nursing lactating females expressed strong Fos‐ir in neurons of the ARC compared to diestrous females. Fos‐ir was encountered in neurons not belonging to the TIDA system and that was for a large proportion identical to the POMCergic neurons.We showed that, in lactating females submitted to suppression of the suckling stimulus by removal of the pups, the pattern of expression of Fos‐ir is similar to that seen in diestrous females and that, a pattern of expression of Fos‐ir indistinguishable from that observed during free lactation is reinstated a short time after the return of the pups and restoration of the suckling stimulus, suggesting that this expression of Fos‐ir strictly depends upon the presence of the newborns and the suckling stimulus. By lowering circulating levels of the PRL with bromocryptine‐or PRL antiserum‐treatment, we noticed a decrease in the number of (β‐endorphin+Fos)‐ir neurons compared to non‐injected freely nursing lactating females. By maintaining high levels of circulating PRL with haloperidol‐treatment, we observed a number of colocalizations close to that observed in freely nursing lactating females. Our results suggest that during lactation a rostral subgroup of the arcuate POMCergic neuronal population is activated at least partially in response to the suckling‐induced secretion of PRL and that this activation participates in maintaining the endocrine and/or metab

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04676.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

This paper describes the development of a new technique to measure melatonin contents in the pineal gland of moving sheep: the microdialysis. A dialysis probe was used to collect extracellular fluid in the sheep pineal gland, but also to inject directly into it different drugs such as isoproterenol at a very low concentration. The probe was implanted the day before the beginning of the experiment in order to obtain low levels of melatonin. This technique makes it possible to measure melatonin in the dialysate and plasma of rams submitted to 8L:16D. No melatonin either in the dialysate or in the plasma was found during the light phase. Shortly after lighting off, the melatonin concentration increased in the dialysate and plasma and remained stable during the dark phase. Melatonin concentrations began to decrease before lighting on and no detectable levels were found during the following light phase. The secretion of melatonin is, at least, under adrenergic regulation. Local infusion of isoproterenol (90 μl at 10−6M), an agonist of β adrenergic receptor, through the probe, increased melatonin levels during 2 h, even when infusions were repeated 3 times. This demonstrates the presence of β adrenergic receptors. The technique presented in this paper could be of considerable interest for studying sheep pineal gland and its main secretion, melatonin, for example during diurnal rhythms or for studying its re

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04667.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY

摘要:

A solution‐hybridization S1‐nuclease protection assay was used to evaluate the expression of messenger RNAs for the activinβAsubunit and type II activin receptor in adult rat brain. Results indicate the presence ofβAsubunit mRNA in both hypothalamus and brainstem, with approximately two‐fold higher levels in brainstem. Levels of activin type II receptor mRNA were similar in the hypothalamus of young virgin and 15‐day lactating females, and in females in which pups were removed after a 5‐day lactation period. Male rats castrated prepubertally (30 days p.n.) had approximately 220% higher (P<0.05) hypothalamic activin type II receptor mRNA levels than postpubertal, 3‐month old age‐matched sham controls. Two month treatment of castrate rats with estradiol (200 ng/g, i.p. every 2 days) reduced hypothalamic activin type II receptor mRNA expression to control levels; the same dose of testosterone had no effect. The expression of the hypothalamic activin type II receptor gene may be estrog

ISSN:0953-8194    

DOI:10.1046/j.1365-2826.1996.04618.x

出版商:Blackwell Science Ltd.    

年代:1996

数据来源: WILEY