Search PubMed⌕ Search

Biomedical subjects

C A Wilson

Publications and source records attributed to C A Wilson.

At least 55 records · Page 3Linked to original sources

Behavioral effects of neuropeptide E-I (NEI) in the female rat: interactions with alpha-MSH, MCH and dopamine.

The behavioral and neurochemical effects of NEI, and its interaction with alpha-MSH or MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) in female rats (bilateral administration, 100 ng in 0.5 microliter/side). NEI in the VMN (but not in the MPOA) stimulated exploratory behavior, increased anxiety and reduced dopamine and DOPAC release. The behavioral effects were antagonized by alpha-MSH. NEI stimulated female sexual receptivity in the MPOA. In the VMN, NEI did not have any effect on sexual activity, but partially antagonized the stimulatory effect of MCH. These results show that NEI in the hypothalamus participates in the regulation of behavior, possibly through dopaminergic mediation.

3,4-Dihydroxyphenylacetic Acid↗

The inter-relationship between gonadal steroids and POMC peptides, beta-endorphin and alpha-MSH, in the control of sexual behavior in the female rat.

Estradiol benzoate (10 microg EB) given to ovariectomized-adrenalectomized rats induced sexual receptivity in half the animals and increased alpha-MSH in the preoptic area, ventromedial nucleus (VMN) and arcuate nucleus (ARC), in all the animals, although levels were significantly higher in the VMN and ARC of the receptive (R) subgroup. EB also raised levels of beta-endorphin in the VMN and ARC in the R rats only. POMC expression was not altered. EB did not affect alphaMSH in extra-hypothalamic areas, but addition of progesterone, raised levels in the septum, amygdala, hippocampus and caudate putamen. Only in the VMN, ARC and septum were the steroid-induced increases correlated with onset of sexual behavior.

Animals↗

Electron microscopic evidence for the mechanism of blood-retinal barrier breakdown in diabetic rabbits: comparison with magnetic resonance imaging.

Diabetes leads to a breakdown of the blood-retinal barrier (BRB), which can be demonstrated in experimental models by immunocytochemistry and magnetic resonance imaging (MRI). The present study utilizes these methods to investigate the mechanism of BRB breakdown in diabetic rabbits, a model ideally suited to both procedures. Rabbits were treated with alloxan and examined 2 months, 1 year, and 1.5 years after the development of diabetes to assess BRB breakdown using MRI and immunocytochemical staining for endogenous albumin. Using MRI, an increased incidence of retinal vascular leakage is first evident at 1 year of diabetes. Electron microscopic immunolocalization of albumin suggests that BRB compromise is principally mediated by transendothelial transport of serum proteins in endocytic vesicle-like structures of approximately 0.4-1 micron diameter. Some additional retinal vascular leakage is occasionally demonstrated through the interendothelial cell tight junctions, but only when adjacent vascular endothelial cells show degenerative changes. The similarity of these findings to those previously reported for diabetic humans and rats supports the use of the diabetic rabbit as a model for studying BRB dysfunction. MRI and electron microscopic (EM) immunocytochemistry are complementary methods for evaluating BRB dysfunction. MRI can provide an overall picture of the entire eye without sacrificing the animal. EM immunocytochemistry can provide a more detailed picture of a limited area of interest to gain insight into the mechanisms of extravasation. Together, both methods provide a more complete understanding of BRB breakdown in diabetic rabbits.

Albumins↗

Simian sarcoma-associated virus fails to infect Chinese hamster cells despite the presence of functional gibbon ape leukemia virus receptors.

We have sequenced the envelope genes from each of the five members of the gibbon ape leukemia virus (GALV) family of type C retroviruses. Four of the GALVs, including GALV strain SEATO (GALV-S), were originally isolated from gibbon apes, whereas the fifth member of this family, simian sarcoma-associated virus (SSAV), was isolated from a woolly monkey and shares 78% amino acid identity with GALV-S. To determine whether these viruses have identical host ranges, we evaluated the susceptibility of several cell lines to either GALV-S or SSAV infection. GALV-S and SSAV have the same host range with the exception of Chinese hamster lung E36 cells, which are susceptible to GALV-S but not SSAV. We used retroviral vectors that differ only in their envelope composition (e.g., they contain either SSAV or GALV-S envelope protein) to show that the envelope of SSAV restricts entry into E36 cells. Although unable to infect E36 cells, SSAV infects GALV-resistant murine cells expressing the E36-derived viral receptor, HaPit2. These results suggest that the receptors present on E36 cells function for SSAV. We have constructed several vectors containing GALV-S/SSAV chimeric envelope proteins to map the region of the SSAV envelope that blocks infection of E36 cells. Vectors bearing chimeric envelopes comprised of the N-terminal region of the GALV-S SU protein and the C-terminal region of SSAV infect E36 cells, whereas vectors containing the N-terminal portion of the SSAV SU protein and C-terminal portion of GALV-S fail to infect E36 cells. This finding indicates that the region of the SSAV envelope protein responsible for restricting SSAV infection of E36 cells lies within its amino-terminal region.

Amino Acid Sequence↗

Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells.

As part of the evaluation of porcine cells, tissues, and organs intended for transplantation into humans, we investigated the conditions required to induce expression and release of porcine endogenous retrovirus (PoEV) from primary cells. Pigs contain endogenous retroviral sequences encoding infectious retrovirus, yet little is known about the conditions required to activate the expression and release of PoEV from primary cells. We show here that mitogenic activation of peripheral blood mononuclear cells (PBMC) isolated from the National Institutes of Health (NIH) miniature pig and the Yucatan pig resulted in the activation and release of an infectious type C retrovirus. Coculture of activated porcine PBMC with pig or human cell lines resulted in the transfer and expression of PoEV-specific sequences and the establishment of a productive infection. Sequence comparison of portions of the PoEV pol gene expressed in pig cell lines productively infected with virus derived from NIH miniature pig and Yucatan pig PBMC revealed marked similarity, suggesting that one or a few loci may be capable of being activated to yield an infectious virus. These findings demonstrate that the presence of endogenous viruses in source animals needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.

Animals↗

Entry of amphotropic murine leukemia virus is influenced by residues in the putative second extracellular domain of its receptor, Pit2.

Human cells express distinct but related receptors for the gibbon ape leukemia virus (GALV) and the amphotropic murine leukemia virus (A-MuLV), termed Pit1 and Pit2, respectively. Pit1 is not able to function as a receptor for A-MuLV infection, while Pit2 does not confer susceptibility to GALV. Previous studies of chimeric receptors constructed by interchanging regions of Pit1 and Pit2 failed to clarify the determinants unique to Pit2 which correlate with A-MuLV receptor function. In order to identify which regions of Pit2 are involved in A-MuLV receptor function, we exchanged the putative second and third extracellular domains of Pit1, either individually or together, with the corresponding regions of Pit2. Our functional characterization of these receptors indicates a role for the putative second extracellular domain (domain II) in A-MuLV infection. We further investigated the influence of domain II with respect to A-MuLV receptor function by performing site-specific mutagenesis within this region of Pit2. Many of the mutations had little or no effect on receptor function. However, the substitution of serine for methionine at position 138 (S138M) in a Pit1 chimera containing domain II of Pit2 resulted in a 1,000-fold reduction in A-MuLV receptor function. Additional mutations made within domain II of the nonfunctional S138M mutant restored receptor function to nearly wild-type efficiency. The high degree of tolerance for mutations as well as the compensatory effect of particular substitutions observed within domain II suggests that an element of secondary structure within this region plays a critical role in the interaction of the receptor with A-MuLV.

Amino Acid Sequence↗

Effects of DPDPE (a specific delta-opioid receptor agonist) and naloxone on hypothalamic monoamine concentrations during the pre-ovulatory LH surge in the rat.

We have investigated the inter-relationship between the opioid and aminergic systems in the control of secretion of the pro-oestrous LH surge and the involvement of delta-opioid receptor subtypes in this process. Conscious female rats bearing a cannula in the femoral artery were injected i.p. with a selective delta-opioid receptor agonist (DPDPE) either alone or with the opioid antagonist (naloxone) at 1300 h on the day of pro-oestrus. Blood samples were collected hourly between 1500 h and 1900 h, and plasma LH levels were measured by RIA. At the end of this period (1900 h), the animals were autopsied and the concentrations of the amines (noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT)) and their metabolites (dihydroxyphenolglycol (DHPG) and 5-hydroxyindoleacetic acid (5HIAA), metabolites of NA and 5HT respectively) were determined by HPLC with electrochemical detection in the medial preoptic area, suprachiasmatic nucleus, median eminence and arcuate nucleus. DPDPE abolished the LH surge and concomitantly decreased hypothalamic NA and DHPG concentrations in all the areas examined. The levels of DA, 5HT and 5HIAA were also reduced in all hypothalamic regions studied, except DA and 5HIAA in the suprachiasmatic nucleus. Naloxone reversed these inhibitory effects of the delta-agonist. We conclude that activation of delta-opioid receptors may exert an inhibitory effect on LH release. The effect is probably an indirect one mediated by the monoaminergic systems, as they are suppressed by DPDPE in nearly all the hypothalamic regions studied.

Animals↗

Diet-induced loss of cyclic ovarian function at normal body weight in a rodent model for bulimia nervosa.

A bulimic rat model was used to test whether type and frequency of food intake mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce an effect on glycoprotein (LH) structure, or affect both processes and if so, to determine whether any such effects were acute, or persisted after return to normal eating patterns. Voluntary hyperphagia was induced by offering female rats a varied and palatable choice of human food items--the 'cafeteria diet'. There were four groups: control (normal chow), obese (continuous cafeteria diet), post-obese (cafeteria diet, then fasted to reduce weight to that of controls) and binge (cafeteria alternated with normal diet every few days). Animals were maintained on these diets for 60 days (phase I). They were then given a GnRH challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of the animals in each group were killed for assessment of effects on their reproductive organs. The remaining animals were returned to normal diets and kept for a further 40 days, when the GnRH challenge was repeated and the animals were killed 24 h later (phase II). All animals on the cafeteria diet in phase I exhibited significant disruption of oestrous cyclicity irrespective of body weight. LH released in response to the first GnRH challenge showed a prolonged half-life, and/or increased rate of secretion in the obese and post-obese groups but in the binge group the secretory/clearance properties resembled those of control animals. After the second GnRH challenge at the end of phase II, however, the LH of the binge group appeared to have different secretory or clearance characteristics, whereas that of the previously obese animals had returned to normal. These data show ovarian cyclicity was disrupted by hyperphagia and irregular eating, even at normal body weight. Relating ovarian function to pituitary output in terms of LH, the effects of the continuous cafeteria diet did not appear to persist in the animals that returned to normal diets, but in the binge group the effect, presumably of the diet manipulation, was manifested after return to a normal eating pattern. This finding suggests that irregular eating habits may exert a direct (and acute) effect on the ovary, but that effects on the pituitary (and LH glycoforms) take longer to be expressed, explaining many features of bulimia nervosa.

Analysis of Variance↗

Update on antiobesity drugs.

The Society for Medicines Research organized a one-day meeting on antiobesity drugs on March 26, 1998, in London. Current environmental risks for obesity include an increase in the proportion of fat consumption--especially an increase in the fat-to-carbohydrate ratio--and an increase in a sedentary life-style without an appropriate lowering in food intake. Energy balance plays a pivotal role of in the control of body stores. Knowing the mechanisms of the control of energy intake and energy expenditure provides explanations for the incidence of obesity and also possible sites for drug intervention. The genetic basis for obesity is complex, with the probability of a number of interacting genes being involved (polygenic inheritance). Each of the main components of the energy balance relationship has a distinct genetic basis. The ob gene was first identified in 1994 by Friedman, and its product is leptin, which may well be a potential target for obesity treatment. Speakers at the meeting highlighted various targets that hold promise in developing pharmacological treatments for obesity: increasing the activity of satiety factors (CCK-8, GPL-1, ACTH, alphaMSH and 5-HT acting on 5-HT(2C) receptors); inhibiting orexigenic agents (NPY, MCH, galanin); targeting thermogenesis (beta(3)-adrenergic agonists and uncoupling proteins); targeting fat absorption; and targeting neuropeptides. Some of the compounds developed to act on these sites are now becoming available.

Journal Article↗

Evaluation of recommendations for replication-competent retrovirus testing associated with use of retroviral vectors.

With input from the gene therapy community, CBER is actively examining the recommendations for RCR testing during retroviral vector production, production of ex vivo-transduced cells, and in patients who receive such material. Our initial recommendations were made at a time when our experience with RCR detection assays and clinical use of retroviral vectors was limited. As the gene therapy field has matured, there is an increasing amount of data available on RCR detection assays and from monitoring of patients in clinical trials. The cumulative data give assurance that RCR detection assays in use are of sufficient sensitivity to provide a margin of safety to patients: no patients to date have evidence of RCR infection. However, CBER encourages members of the gene therapy community to continue to submit data to the FDA or to publish data that will enhance the cumulative data base on RCR testing assays, experience with different VPC, and patient monitoring. Based on the analysis of data accumulated to data, and ongoing discussions with members of the gene therapy community, CBER is proposing to discuss changes to the current RCR testing recommendations, as summarized below. RCR testing during production of retroviral vector and ex vivo-transduced cells. Development of characterized standards for RCR testing of supernatant and cells should allow comparison of assay sensitivity. One proposal under consideration is to apply statistical methods to determine how much material needs to be tested independent of the size of the production lot. Data and discussion are still needed to define a limit concentration and a value for probability of detection for RCR testing, while maintaining an appropriate margin of safety. These modifications of RCR testing strategies could lead to improvements in assay sensitivity. Additional discussion and data are also needed to evaluate the current recommendations of the testing for ex vivo-transduced cells: should both cells and supernatant be tested in all cases? RCR testing during patient follow-up. The time points required for RCR testing during patient follow-up need examination. One proposal under consideration is to sample and assay at three time points during the first year of treatment (e.g., 4-6 weeks, 3 months, and 1 year post-treatment). Further discussion is needed to define appropriate additional follow-up. Choice of assays to detect surrogate markers for RCR infection (i.e., serologic or PCR-based assays) should consider mode of vector administration and the patient population. Positive results with such assays should be pursued by direct culture assay to obtain and characterize the infectious viral isolate. These proposals will be the focal point for the discussion at the Retroviral Vector Breakout Session at the 1997 FDA/NIH Gene Therapy Conference. After the 1997 FDA/NIH Gene Therapy Conference, CBR plans to propose revised recommendations for RCR testing for public comment.

Cell Transformation, Viral↗

Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-delta11b.

The mechanism of BRCA1 tumor suppression in human breast and ovarian cells is the focus of intense investigation. In this report, full length BRCA1 (230 kDa) introduced into cells with CMV promoter constructs was nuclear when transgene expression was low whereas high expression resulted in cytoplasmic accumulation, aberrant nuclear and cell morphology. A nuclear localization signal (NLS) was mapped to BRCA1 amino acid positions 262-570. We describe a splice variant, BRCA1-delta11b, missing the majority of exon 11 including the NLS. Exogenous BRCA1-delta11b (110 kDa) was cytoplasmic and, unlike the full-length protein, overexpression of the protein encoded by the variant did not appear to be toxic. RNA probe titrations and RT-PCR demonstrated that BRCA1 and delta11b transcripts are coexpressed in a wide variety of cells and tissues. Interestingly, BRCA1-delta11b message was greatly reduced or absent in several breast and ovarian tumor lines relative to exon 11 transcripts and a delta9,10 splice variant. Taken together our results suggest that full-length BRCA1 and BRCA1-delta11b may have distinct roles in cell growth regulation and tumorigenesis.

Alternative Splicing↗

Effect of transient cerebral ischemia on gamma-aminobutyric acidA receptor alpha 1-subunit-immunoreactive interneurons in the gerbil CA1 hippocampus.

Following transient cerebral ischemia, pyramidal cells within area CA1 of the hippocampus exhibit delayed neuronal death. While interneurons within this sector continue to survive long-term, there is evidence that some interneurons in area CA1 are vulnerable to damage. To determine the nature of vulnerability in a neurochemically heterogeneous population of interneurons throughout area CA1, we examined the labeling of gamma-aminobutyric acid (GABA)ergic interneurons with an antibody to the GABAA receptor alpha 1-subunit 1-35 days following cerebral ischemia in the Mongolian gerbil. Unlike some other GABA interneuron markers, this antibody labels both the dendrites and soma of interneurons, allowing dendritic structure to be examined. Three to four days following ischemia, the pyramidal cells in area CA1 had degenerated, and the alpha 1-subunit-positive interneurons in all layers of area CA1 had developed severely beaded dendrites. At longer survival times (21-35 days), the alpha 1-subunit-immunolabeled dendrites of these interneurons had a fragmented appearance. In contrast, interneurons bordering str. oriens and alveus typically exhibited normal dendritic morphology. Despite the pathologic changes, there was no evidence of interneuron loss in area CA1 up to 35 days post-ischemia. Normal interneuron morphology was also observed in area CA3 and dentate gyrus, regions where neither pyramidal neurons nor granule cells, respectively, die following 5 min of cerebral ischemia. To determine if the ischemia-induced changes in interneuron morphology could be prevented, diazepam was administered 30 and 90 min following ischemia. Diazepam produces long-term neuroprotection of area CA1 pyramidal neurons. In gerbils sacrificed 35 days after ischemia, diazepam markedly attenuated the dendritic beading of the area CA1 interneurons. In addition, the dendrites did not display the fragmented labeling by the alpha 1-subunit antibody. Thus, despite their long-term survival, CA1 hippocampal interneurons in the gerbil can express severe structural abnormalities after transient cerebral ischemia coincident with pyramidal cell degeneration, and the injury to the dendrites can be prevented by the neuroprotectant diazepam.

Animals↗

A comparative study of the effects of argon and diode laser photocoagulation on retinal oxygenation.

BACKGROUND: The purpose of this study was to compare the effects of diode and argon laser photocoagulation (DLP and ALP) on the preretinal oxygen tension (PO2): (1) directly over photocoagulated retina and (2) in between laser lesions. METHODS: DLP or ALP was applied to avascular rabbit retina to produce grade II lesions. On the day of the oxygen measurement, a droplet of perfluorotributylamine was placed into the preretinal vitreous space over the lasered area of retina and the steady-state PO2 was measured in normoxic animals using 19F magnetic resonance spectroscopy. To determine the PO2 directly over laser lesions, small (5-microliter) droplets were placed over large (approximately 4 mm x 5 mm), confluent areas of treatment (burn area approximately 95% of the treated retinal surface area). To determine the PO2 in between laser lesions, a large (10-microliter) droplet was placed over a field of scatter photocoagulation (burn area approximately 30% of the treated retinal surface area). The theoretical basis for this approach is discussed. RESULTS: Untreated eyes had a preretinal PO2 of 22 +/- 9 mm Hg (mean +/- SD, n = 15 eyes). The preretinal PO2 was significantly higher over confluent, 12-day-old ALP or DLP lesions (51 +/- 13 mm Hg, n = 8 eyes; P < 0.01) compared to untreated eyes. However, at that time, DLP lesions had significantly higher PO2 values (60 +/- 13 mm Hg, n = 4 eyes) than did ALP lesions (42 +/- 6 mm Hg, n = 4 eyes; P = 0.04). The preretinal space in between laser lesions generally showed no significant increase in PO2 (P > 0.05) over controls on post-treatment days 1, 5, 14 and 47. The only exception was in the DLP group of eyes, in which a significant increase in PO2 over untreated or ALP-treated eyes occurred on post-treatment day 5 (41 +/- 7 mm Hg, n = 5 eyes; P = 0.01). Over photocoagulation lesions in this study, DLP produced a greater increase in preretinal PO2 compared to control values than did ALP. CONCLUSIONS: These results support the use of DLP as an alternative to ALP for the treatment of retinal vascular diseases in which hypoxia is suspected to play a role.

Animals↗

alpha-Melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating hormone (MCH) modify monoaminergic levels in the preoptic area of the rat.

The effect of perfusion of melanin-concentrating hormone (MCH) or alpha-melanocyte-stimulating hormone (alpha-MSH) (100 ng/microliter) in the ventromedial nucleus (VMN) or medial preoptic area (MPOA) on monoaminergic levels of female rats was measured using microdialysis and HPLC-electrochemical detection. In the MPOA, alpha-MSH raised 5-HIAA concentration, whereas MCH reduced both 5-HT and 5-HIAA. Neither peptide had any effect in the VMN. The opposite effects of the peptides on the serotonergic system might be responsible for their antagonistic or opposite actions previously reported on several CNS functions. Dopamine may mediate the similar effects of the two peptides, because alpha-MSH inhibits dopaminergic release in the MPOA (but not VMN) and MCH tends to follow the same pattern.

Animals↗

Relationship of the white blood cell count to body fat: role of leptin.

The white blood cell (WBC) count is correlated to the amount of body fat in humans, but the mechanism for this association is unknown. Leptin, a 16 kD protein produced in adipocytes, circulates in humans in direct proportion to the amount and percentage of body fat. Recent evidence suggests that leptin and the leptin receptor are part of a novel pathway which stimulates haemopoiesis. This study was designed to test whether fasting plasma leptin concentrations contribute to the relationship between the WBC count and body fat. 117 Pima Indians with a wide range in body composition were studied. The WBC count was positively correlated with percentage of body fat (r = 0.44, P = 0.0001) and fasting plasma leptin concentration (r = 0.38, P = 0.0001). In multiple regression analyses, age, gender and percent body fat were significant independent determinants of the WBC count. After controlling for age and gender, percent body fat accounted for 23% of the variance in the WBC count (partial r = 0.48, P = 0.0001). In similar models which also included plasma leptin concentration, percent body fat remained significantly related to the WBC count. but only accounted for 7% of its variance (partial r = 0.27, P = 0.003). Based on these results, and the demonstration that leptin directly effects the stimulation of proliferation of haemopoietic stem cells in vitro, we hypothesize that the relation of the WBC count to percent body fat may be mediated, in part, through the effect of leptin.

Adipose Tissue↗

Influence of the cannulated vitrectomy system on the occurrence of iatrogenic sclerotomy retinal tears.

PURPOSE: To determine whether the use of the cannulated vitrectomy system decreases the incidence of sclerotomy-related retinal tears relative to traditional vitrectomy techniques. METHODS: Forty-one eyes of 77 patients in this study were randomly selected to undergo treatment with the cannulated port system. RESULTS: We demonstrated a statistically significant decreased incidence of sclerotomy tears in the cannulated group relative to the noncannulated group (1% vs. 7.7%, P < 0.05). The benefit of the cannulated port system appears to be greatest in cases in which an inexperienced surgeon is learning the techniques of vitreoretinal surgery, in eyes with a preoperative diagnosis of tractional diabetic detachment, and in surgery requiring membrane delamination (simple and extensive). CONCLUSION: The three-port vitrectomy system decreases the incidence of sclerotomy-related retinal tears.

Catheterization↗

Stimulatory effect of melanin-concentrating hormone on luteinising hormone release.

Alpha-melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating hormone (MCH) are two peptide neurotransmitters widely distributed in the mammalian brain, the former originating mainly from cell bodies in the arcuate nucleus and the latter from cell bodies in the zona incerta and lateral hypothalamus. Within the hypothalamus they innervate the pre-optic area, median eminence (ME) and ventromedial nucleus (VMN). Both peptides stimulate sexual behaviour and in this report we have investigated their effect on another gonadal steroid-dependent function, luteinising hormone (LH) release. alpha-MSH, MCH or a combination of the two were injected bilaterally (100 ng/side) into either the medial pre-optic area (MPOA), ME, or VMN of anaesthetised (Saffan 3 ml/kg i.p.) rats that had previously been ovariectomised and adrenalectomised (O+A) and then primed with 5 microg/rat s.c. oestradiol benzoate (OB), 48 h before peptide administration. MCH stimulated LH release when applied to the MPOA and ME; alpha-MSH was inhibitory in the ME and in this model was ineffective in the MPOA. Neither peptide was effective in the VMN. The two peptides were then injected into the MPOA of O+A rats primed with OB followed 48 h later by 0.5 mg/rat s.c. progesterone, which normally induces an LH surge. alpha-MSH, but not MCH, inhibited this induced rise in LH. Administration of anti-MCH antiserum (0.5 microg/side neat serum) also had an inhibitory effect on LH release in this model. These results show that MCH has a stimulatory effect on LH release when administered into the ME and MPOA. In the MPOA, this may be physiologically significant since blocking endogenous MCH with an anti-MCH antiserum inhibits LH release. On the other hand, alpha-MSH has an inhibitory effect on LH release in the MPOA and ME. In the teleost skin these two peptides are functionally antagonistic; it seems that a similar antagonism exists between their effects on LH release.

Adrenalectomy↗

Comparison of serotonin receptor numbers and activity in specific hypothalamic areas of sexually active and inactive female rats.

In a previous study we have shown that a positive correlation exists between 5-hydroxytryptamine (5-HT) activity and female sexual receptivity in the pre-optic area (POA) and median eminence (ME) and that there is a negative correlation in the ventromedial nucleus (VMN), zona incerta (ZI) and arcuate nucleus (ARC). In this report, the possibility that 5-HT receptor density and affinity alter with sexual receptivity has been investigated. Micropunches of the POA, VMN, ARC, ME and the anterior hypothalamus were dissected from ovariectomised rats primed with a submaximal steroid regime (2 microg oestradiol benzoate, OB, followed at 48 h by 0.05 mg progesterone) which induced receptivity (lordosis quotient, LQ, 80-100%) in approximately half the animals, the remaining half usually exhibiting an LQ <20%. Binding studies were carried out using 3H-ketanserin (5-HT2A ligand) and 3H-8-hydroxy-2-(di-n-propylamine)tetraline (8-OHDPAT; 5-HT1A ligand) and pooled (n = 5) micropunch samples. The Bmax of 5-HT2A receptors in the sexually receptive groups was significantly (p < 0.05) greater in the POA and ME and significantly lower in the VMN, ARC and ZI when compared with values in the non-receptive animals. The KD values of the 5-HT2A receptors did not differ in the two groups (except the ZI, where the KD was lower in receptive rats). Neither the Bmax nor KD of the 5-HT1A receptors differed in the two groups in any area investigated. Administration of the 5-HT2 agonists dimethoxyiodophenylaminopropane and m-chlorophenyl piperazine into the POA resulted in enhanced sexual activity in animals exhibiting a low level of receptivity, after 5 microg OB given alone while ketanserin (5-HT2A antagonist) in the POA inhibited sexual activity in receptive animals primed with the submaximal steroid regime given above. In the same models, neither the 5-HT2 agonists nor the 5-HT2A antagonist affected behaviour when applied to the VMN. The 5-HT1A agonist 8-OHDPAT exerted an inhibitory effect in the VMN. These findings, together with earlier results, show that in receptive animals there is an increase in both 5-HT turnover and 5-HT2A receptors in the POA and ME. Additionally 5-HT2 agonists and an antagonist applied to the POA enhance and reduce sexual activity, respectively. This suggests that the 5-HT2 system in the POA has a stimulatory role in the control of female sexual behaviour. Both 5-HT activity and 5-HT2 receptors are decreased in the VMN, ARC and ZI of receptive animals. 5-HT2 agonists and a 5-HT2A antagonist have no effect in the VMN indicating that there is no 5-HT2-stimulatory or -inhibitory effect in this area, at least in the animal models used in these experiments. However, the VMN is a site of an inhibitory action mediated by the 5-HT1A receptors.

Animals↗