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Biomedical subjects

C J Scott

Publications and source records attributed to C J Scott.

At least 19 recordsLinked to original sources
PubMed2005

Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome.

OBJECTIVE: Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was addressed by studying the steroid hormone changes in women with PCOS with either high or normal LH levels leading to inferences regarding the primacy of elevated LH in the pathophysiology of PCOS. METHODS: A cross-sectional study was designed in an academic clinical facility involving 234 women with PCOS. Patients were divided into two groups based on an LH/FSH ratio < or >1 and hormonal and metabolic studies were performed in both groups. Factors were determined by binomial logistic regression that predicted group membership of these women. RESULTS: Higher follicular phase estradiol (E2) and androstenedione (A4) levels as well as greater insulin sensitivity were the only factors that predicted the presence of neuroendocrine dysfunction with elevated A4 being necessary for neuroendocrine dysfunction. CONCLUSIONS: It was concluded that uncoupling of hypothalamic E2 inhibition by elevated ovarian A4 associated with E2 related sensitization of pituitary LH leads to neuroendocrine dysfunction in PCOS.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Breast cancer management: the perspective of general practitioners in inner and eastern Melbourne.

This study sought to explore general practitioners' (GPs') experience with specialist breast services and to identify their communication, education and resource requirements regarding care of the breast cancer patient, by means of a self-administered questionnaire distributed to 450 GPs in inner and eastern Melbourne. Twenty-three per cent of questionnaires were returned. On average, GPs had one patient newly diagnosed with breast cancer per year. GPs were most likely to refer symptomatic patients to a private specialist breast surgeon. Their referral pattern was largely influenced by previous experience of referral to the service. Communication with specialist breast services was generally satisfactory during the initial stages of diagnosis and treatment; however discharge communication, phone communication with specialists, and admission notification was less satisfactory. When given a list of topics in which GPs may require further education, 65% of respondents identified "Recent advances in breast cancer management" as an area of interest, and the majority requested a directory listing breast services in their local area.

Breast Neoplasms↗
PubMed2004

Sex differences in the distribution and abundance of androgen receptor mRNA-containing cells in the preoptic area and hypothalamus of the ram and ewe.

Rams and ewes show a negative-feedback response to peripheral treatment with testosterone, with both sexes having a similar degree of suppression in luteinizing hormone (LH) secretion during the breeding season. At least part of the action of testosterone to suppress gonadotropin-releasing hormone/LH secretion is exerted via interaction with an androgen receptor. The distribution of androgen receptor-containing cells in the hypothalamus has been described for the ram, but similar studies have not been performed in the ewe. In the present study, we tested the hypothesis that levels of androgen receptor mRNA expression in the preoptic area and hypothalamus would be similar in rams and ewes. Perfusion-fixed brain tissue was obtained from adult Romney Marsh ewes (luteal phase) and rams during the breeding season (n = 4/sex). Androgen receptor mRNA expression was quantified in hypothalamic sections by in situ hybridization using an (35)S-labelled riboprobe and image analysis. Hybridizing cells were found in the medial preoptic area, bed nucleus of the stria terminalis, anterior hypothalamic area, ventromedial nucleus, arcuate nucleus and premamillary nucleus. The level of androgen receptor mRNA expression was higher in rams than ewes in the rostral preoptic area, caudal preoptic area and rostral portion of the bed nucleus of the stria terminalis, with no sex difference in other regions. The preoptic area and bed nucleus of the stria terminalis are important for reproductive behaviour and the sex differences in androgen receptor mRNA expression at these levels may relate to this. The high level of androgen receptor mRNA expression in the basal hypothalamus, with no sex difference, is consistent with the role of this region in the regulation of gonadotropin secretion.

Animals↗
PubMed2001

Noradrenergic projections from the A1 field to the preoptic area in the brain of the ewe and Fos responses to oestrogen in the A1 cells.

Previous studies have shown that there is a population of noradrenergic cells in the caudal A1 field of the brainstem of the ewe that contain oestrogen receptors and project to the preoptic area, where gonadotrophin releasing hormone (GnRH) neurones are located. There are some discrepancies in the literature regarding the extent of this projection and the location of the cells in the A1 region. The issue has been a focus of attention because the positive feedback response to oestrogen that causes the ovulatory GnRH/luteinizing hormone surge may originate from this brainstem region. The aim of the present study was to determine the extent of the projections to the preoptic area and to determine whether the caudal A1 cells are activated by oestrogen. Eleven ovariectomized ewes received an injection of the retrograde tracer FluoroGold into the preoptic hypothalamus and four of these also received an i.m. injection of oestrogen 2 h before tissue collection. A further three sheep received i.m. oil injections to act as controls for those receiving oestrogen. Dopamine-beta-hydroxylase (DBH)-positive, retrogradely labelled cells were found within the A1 field in sheep that received preoptic FluoroGold injections. Cells in the vicinity of the A2 and A6 fields, that were retrogradely labelled with FluoroGold, were not DBH-positive. Thus, cells in the A1 field provide a direct noradrenergic projection to the preoptic area and may be involved in the control of the secretion of GnRH in this species. Cells that project to the preoptic hypothalamus from more rostrally located areas of the brainstem are not noradrenergic. In the animals that received oestrogen, double-labelling immunohistochemistry was performed throughout the A1 field for FluoroGold, DBH and Fos. DBH cells of the A1 field expressed Fos only in the oestrogen-treated animals and not in the oil-treated animals. There was a decline in the number of DBH cells that were retrogradely labelled from the caudal region of A1 towards obex. There was a similar gradient in the number of cells that were double-labelled for Fos and FluoroGold. We conclude that there is a population of noradrenergic cells in the caudal A1 field that project to the preoptic area; this is a larger group of cells than previously reported. Oestrogen elicits an acute Fos response in these cells, which may be involved in the time-delayed positive feedback response on GnRH cells. The caudal-to-rostral gradient in the labelling with FluoroGold and Fos in DBH-positive cells is similar to that seen previously for oestrogen receptor in DBH-positive cells in the A1 field.

Animals↗
PubMed2001

Changes in preoptic and hypothalamic levels of progesterone receptor mRNA across the oestrous cycle of the ewe.

We measured the levels of progesterone receptor (PR) mRNA in the hypothalamus and preoptic area (POA) of the ewe across the oestrous cycle. Perfusion-fixed hypothalamic tissue was collected from sheep killed during the luteal and follicular phases and during behavioural oestrus. Blood samples taken at the time of tissue collection verified that the oestrous ewes were undergoing a preovulatory luteinizing hormone (LH) surge. Matched sections were taken from the POA, periventricular nucleus (PeVN), ventromedial nucleus (VMN) and arcuate nucleus of each animal. In situ hybridization was performed using a sheep specific, (35)S-labelled riboprobe for PR and semiquantitative image analysis was conducted on emulsion-dipped slides. The number of silver grains per cell was greater in the VMN and arcuate nucleus of oestrous ewes than in luteal and follicular phase ewes; there was no cyclic variation in the level of PR mRNA expression in the cells of the POA and PeVN. The number of labelled cells per mm2 in the VMN was higher in the oestrous ewes than in luteal phase and follicular phase ewes. The number of labelled cells in the PeVN was also higher in the oestrous ewes than in follicular phase ewes, but there was no cyclic variation in the POA and arcuate nucleus. In the ewe, the onset of behavioural oestrus corresponds to the onset of the preovulatory LH surge and increased PR mRNA expression at this time is likely to be due to the high concentrations of circulating oestrogen that precede this period.

Animals↗
PubMed2001

Cells of the arcuate nucleus and ventromedial nucleus of the ovariectomized ewe that respond to oestrogen: a study using Fos immunohistochemistry.

Oestrogen produces a positive feedback effect on the secretion of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) when implanted into the ventromedial/arcuate nucleus of the ovariectomized (OVX) ewe. This has led to the belief that it is in this area of the hypothalamus that oestrogen causes the preovulatory surge in GnRH/LH. To date, however, the cell types that are integral to this response have not been identified. The present study aimed to examine cellular responsiveness to oestrogen in this region of the brain using Fos immunohistochemistry and further aimed to determine the cell type that shows an acute response to oestrogen. OVX ewes (n = 4-6 per group) were given i.m. injections of oestradiol benzoate or oil (vehicle) and were killed 1-6 h later. Brains were perfused for immunohistochemistry. The number of cells in the arcuate nucleus which were immunopositive for Fos was greater (two- to fourfold) in the oestradiol benzoate-treated OVX ewes (n = 5) 1 h after injection. The number of Fos-positive cells in the ventromedial hypothalamic nucleus was 10-fold greater in the oestradiol benzoate-treated ewes 1 h after injection. Because there were high levels of Fos-immunoreactive cells in oil-treated ewes, we repeated the experiment with i.v. injection of 50 microg oestrogen or vehicle (n = 5). With this latter procedure, we found that oestrogen injection caused a significant increase in the number of Fos immunoreactive cells in the arcuate nucleus within 1 h, but there was no response in the ventromedial hypothalamus. To further characterize the types of cells that might respond to oestrogen, we double-labelled cells for Fos and either adrenocorticotropin hormone, neuropeptide Y or tyrosine hydroxylase (a marker for dopaminergic cells). These cell types could account for less than 30% of the total number of cells that were Fos-positive and oestrogen treatment did not cause an increase in the Fos labelling of any of these types of cell. These data show that oestrogen activates cells of the arcuate/ventromedial hypothalamus within 1 h of injection and that this response could relate to the feedback effects of this gonadal hormone. The majority of cells that produce Fos following oestrogen injection are of unknown phenotype. The data further suggest that induction of cells of the ventromedial hypothalamic nucleus require more prolonged oestrogen stimulus than cells of the arcuate nucleus.

Adrenocorticotropic Hormone↗
PubMed2001

PCR-based detection and identification of Burkholderia cepacia complex pathogens in sputum from cystic fibrosis patients.

PCR amplification of the recA gene followed by restriction fragment length polymorphism (RFLP) analysis was investigated for the rapid detection and identification of Burkholderia cepacia complex genomovars directly from sputum. Successful amplification of the B. cepacia complex recA gene from cystic fibrosis (CF) patient sputum samples containing B. cepacia genomovar I, Burkholderia multivorans, B. cepacia genomovar III, Burkholderia stabilis, and Burkholderia vietnamiensis was demonstrated. In addition, the genomovar identifications determined directly from sputum were the same as those obtained after selective culturing. Sensitivity experiments revealed that recA-based PCR could reliably detect B. cepacia complex organisms to concentrations of 10(6) CFU g of sputum(-1). To fully assess the diagnostic value of the method, sputum samples from 100 CF patients were screened for B. cepacia complex infection by selective culturing and recA-based PCR. Selective culturing identified 19 samples with presumptive B. cepacia complex infection, which was corroborated by phenotypic analyses. Of the culture-positive sputum samples, 17 were also detected directly by recA-based PCR, while 2 samples were negative. The isolates cultured from both recA-negative sputum samples were subsequently identified as Burkholderia gladioli. RFLP analysis of the recA amplicons revealed 2 patients (12%) infected with B. multivorans, 11 patients (65%) infected with B. cepacia genomovar III-A, and 4 patients (23%) infected with B. cepacia genomovar III-B. These results demonstrate the potential of recA-based PCR-RFLP analysis for the rapid detection and identification of B. cepacia complex genomovars directly from sputum. Where the sensitivity of the assay proves a limitation, sputum samples can be analyzed by selective culturing followed by recA-based analysis of the isolate.

Adolescent↗
PubMed2001

Progesterone and testosterone in combination act in the hypothalamus of castrated rams to regulate the secretion of LH.

We tested the hypotheses that progesterone enhances the negative feedback actions of testosterone in rams and that this occurs through actions at the hypothalamus. In the first part of this study, blood samples were collected every 10 min for 12 h before and after 7 days of treatment (i.m.) of castrated Romney Marsh rams (n=5 per group) with vehicle, progesterone (4 mg/12 h), testosterone (4 mg/12 h) or a combination of progesterone (4 mg/12 h) and testosterone (4 mg/12 h). In the second part of this study the brains of four gonad-intact Romney Marsh rams were collected, the hypothalamus was sectioned and in situ hybridisation of mRNA for progesterone receptors conducted. After 7 days of treatment with vehicle or progesterone or testosterone alone, there were no changes in the secretion of LH. In contrast, treatment with a combination of progesterone and testosterone resulted in a significant (P<0.01, repeated measures ANOVA) decrease in mean plasma concentrations of LH, the number of LH pulses per hour and the pre-LH pulse nadir and a significant (P<0.01) increase in the inter-LH pulse interval. We found cells containing mRNA for progesterone receptors throughout the hypothalamus, including the preoptic area (where most GnRH neurons are located in sheep), the periventricular, ventromedial and arcuate nuclei and the bed nucleus of the stria terminalis. This study shows that progesterone is capable of acting centrally with testosterone to suppress the secretion of LH in castrated rams and that cells containing mRNA for progesterone receptors are located in the hypothalamus of rams in the vicinity of GnRH neurons.

Analysis of Variance↗
PubMed2000

Gonadal steroid receptors in the regulation of GnRH secretion in farm animals.

The sites of action and mechanisms by which gonadal steroids regulate gonadotrophin-releasing hormone (GnRH) in domestic animals remain largely unknown. This review summarises information gained from sheep regarding the distribution of the gonadal steroid receptors in the brain, the neurochemical identity and the projections of these steroid receptor-containing neurones. The cells in the hypothalamus that contain each of the gonadal steroid receptors (oestrogen receptor alpha (ERalpha), oestrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR)) show a remarkably similar distribution, although the PR and AR-containing cells are less widespread than oestrogen receptors (ERs). There is considerable overlap in the distribution of ERalpha- and ERbeta-containing cells but also some unique sites for each subtype. This suggests differential regulation of the actions of oestrogen. There appears to be little sexual dimorphism in the distribution of the gonadal steroid receptors in the hypothalamus, with the notable exception of the ventromedial nucleus where females appear to have greater numbers of both ERalpha- and ERbeta-containing cells. Neuronal tracing studies have identified projections of some of the ERalpha-containing cells to sites that may allow interaction with the GnRH system. The receptor mapping, neuronal tracing and microimplantation studies suggest that the ventromedial nucleus is likely to be a key hypothalamic nucleus in the steroid regulation of GnRH secretion in sheep.

Animals↗
PubMed2000

The distribution of progesterone receptor immunoreactivity and mRNA in the preoptic area and hypothalamus of the ewe: upregulation of progesterone receptor mRNA in the mediobasal hypothalamus by oestrogen.

The distribution of progesterone receptors (PR) was mapped in the hypothalamus of the ewe using immunocytochemistry. These results were confirmed using in situ hybridization with a sheep-specific 35S-labelled riboprobe. In addition, the effect of oestrogen on the level of PR mRNA in the hypothalamus was examined in ovariectomized (OVX) ewes following treatment with an oestrogen implant or without treatment. PR immunoreactive (-ir) cells were readily detected in OVX animals. Labelled cells were observed in four main hypothalamic regions: the preoptic area (POA), including the organum vasculosum of the lamina terminalis, periventricular nucleus (PeVN), ventromedial nucleus (VMN) and the arcuate nucleus (ARC) (including the region ventral to the mamillary recess). In addition, lightly stained PR-ir cells were observed in the supraoptic nucleus and a few PR-ir cells were also found in the diagonal band of Broca. No PR-ir cells were found in the brainstem. PR mRNA-containing cells were found in the same hypothalamic regions as the PR-ir cells. Image analysis of emulsion-dipped slides following in situ hybridization indicated that oestrogen treatment increased (P<0.01) the mean number of silver grains/cell and the density of labelled cells in the VMN and ARC but had no effect on the level of PR mRNA expression in the POA or PeN. The distribution of PR-containing cells in the hypothalamus is similar to that described in other species and all cells were located in nuclei that contain large populations of oestrogen receptor-containing cells. These include regions implicated in the regulation of reproductive neuroendocrine function, and reproductive behaviour. Oestrogen and progesterone synergize to inhibit GnRH secretion and the present results suggest that these functions may involve cells of the VMN and ARC, with oestrogen acting to upregulate PR.

Animals↗
PubMed2000

Seasonal changes in the expression of neuropeptide Y and pro-opiomelanocortin mRNA in the arcuate nucleus of the ovariectomized ewe: relationship to the seasonal appetite and breeding cycles.

Sheep experience well-documented seasonal changes in reproductive activity and voluntary food intake (VFI). Within the hypothalamus, neurones that express neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) have been implicated in the regulation of reproduction and appetite. In this study, we aimed to determine the extent to which the expression of these two neuronal systems is linked to the seasonal reproductive cycle and/or the seasonal appetite cycle. VFI in our sheep reaches a nadir in August with no difference occurring between December and February. We examined the brains of ovariectomized (OVX) female sheep (n=5-7) that were killed during the breeding season (February) or during the early or late nonbreeding season (August and December, respectively). The brains of these animals were perfused with paraformaldehyde and processed for in situ hybridization histochemistry, using ribonucleotide probes labelled with 35S. The number of NPY and POMC cells and the number of silver grains per cell were counted using an image analysis system. For NPY, the number of cells counted in the arcuate nucleus/median eminence region and the number of silver grains per cell was significantly lower in animals killed during August than in animals killed in February or December. The number of grains per cell over NPY cells was also significantly lower in animals killed during August. For POMC, the number of cells was lower in February than in August and December. Similarly, the number of grains per cell for POMC were lower in February than in August and December. VFI was significantly lower in animals during August than at other times of the year. We conclude that in OVX ewes: (i) NPY gene expression is lower at the time of the year when VFI is reduced and (ii) POMC gene expression is greater at the time of the nonbreeding season than during the breeding season. Because these results were obtained in OVX animals, the changes appear to be independent of alterations in the secretion and/or action of ovarian steroids. Thus, the activity of NPY neurones appears to relate to changes in appetite whereas changes in POMC expression may be relevant to the seasonal breeding cycle.

Animals↗
PubMed2000

Protein disulfide isomerase-mediated cell-free assembly of recombinant interleukin-12 p40 homodimers.

Interleukin-12 (IL-12) is a heterodimeric cytokine composed of two subunits, p35 and p40. The disulfide-linked homodimer (p40)2 has been shown to be a potent IL-12 antagonist. In the present study, the p40 subunit was refolded from Escherichia coli inclusion bodies. Formation of (p40)2 was greatly increased in a redox buffer containing reduced and oxidized glutathione, but was not significantly affected by the cosolvents urea, GdnHCl or Chaps. While protein disulfide isomerase (PDI), GroEL/ES or DnaK/J/GrpE suppressed aggregation during refolding of p40, only DnaK/J/GrpE and PDI enhanced p40 dimerization. Oxidative assembly of p40 into (p40)2 by PDI, but not suppression of aggregation, was strongly dependent on inclusion of BSA in the refolding buffer. It is concluded that both chaperone-like and disulfide isomerase effects are essential for correct folding of p40 into dimers.

Amino Acid Sequence↗
PubMed2000

The distribution of cells containing estrogen receptor-alpha (ERalpha) and ERbeta messenger ribonucleic acid in the preoptic area and hypothalamus of the sheep: comparison of males and females.

We have used in situ hybridization to compare the distributions of estrogen receptor alpha (ERalpha) and ERbeta messenger RNA (mRNA)-containing cells in the preoptic area and hypothalamus of ewes and rams. Perfusion-fixed brain tissue was collected from luteal phase ewes and intact rams (n = 4) during the breeding season. Matched pairs of sections were hybridized with sheep-specific, 35S-labeled riboprobes, and semiquantitative image analysis was performed on emulsion-dipped slides. A number of sex differences were observed, with females having a greater density of labeled cells than males (P < 0.001) and a greater number of silver grains per cell (P < 0.01) in the ventromedial nucleus for both ER subtypes. In addition, in the retrochiasmatic area, males had a greater (P < 0.05) cell density for ERalpha mRNA-containing cells than females, whereas in the paraventricular nucleus, females had a greater density (P < 0.05) of ERalpha mRNA-containing cells than males. There was a trend (P = 0.068) in the arcuate nucleus for males to have a greater number of silver grains per cell labeled for ERalpha mRNA. In both sexes, there was considerable overlap in the distributions of ERalpha and ERbeta mRNA-containing cells, but the density of labeled cells within each nucleus differed in a number of instances. Nuclei that contained a higher (P < 0.001) density of ERalpha than ERbeta mRNA-containing cells included the preoptic area, bed nucleus of the stria terminalis, and ventromedial nucleus, whereas the subfornical organ (P < 0.001), paraventricular nucleus (males only, P < 0.05), and retrochiasmatic nucleus (females only, P < 0.05) had a greater density of ERalpha than ERbeta mRNA-containing cells. The anterior hypothalamic area and supraoptic nucleus had similar densities of cells containing both ER subtypes. The lateral septum and arcuate nucleus contained only ERalpha, whereas only ERbeta mRNA-containing cells were seen in the zona incerta. The sex differences in the populations of ER mRNA-containing cells in the ventromedial and arcuate nuclei may explain in part the sex differences in the neuroendocrine and behavioral responses to localized estrogen treatment in these nuclei. Within sexes, the differences between the distributions of ERalpha and ERbeta mRNA-containing cells may reflect differential regulation of the actions of estrogen in the sheep hypothalamus. Low levels of ERbeta mRNA in the preoptic area and ventromedial and arcuate nuclei, regions known to be important for the regulation of reproduction, suggest that ERbeta may not be involved in these functions.

Animals↗
PubMed1999

Levels of dopamine beta hydroxylase immunoreactivity in the preoptic hypothalamus of the ovariectomised ewe following injection of oestrogen: evidence for increased noradrenaline release around the time of the oestrogen-induced surge in luteinizing hormone.

We have measured dopamine beta hydroxylase (DBH) immunoreactivity in the preoptic hypothalamus as an index of release of noradrenaline in the ovariectomised (OVX) ewe at the time of an oestrogen-induced surge in luteinizing hormone (LH) release. OVX ewes (n=5) were given an injection of 50 microg oestradiol benzoate (or oil), which causes a surge in the secretion of LH. Blood samples were taken and sheep were killed 16 h later. Other groups (n=3) were given oil or oestrogen and killed 6 h later. Brains were collected for immunohistochemistry and image analysis. The number of DBH-stained cells and the integrated optical density of the cells was measured throughout the A1 field of the brainstem. The DBH staining was measured in the terminal beds of the hypothalamus. There was no difference between the controls and the EB-treated OVX ewes in the number of DBH positive cells or the optical density of DBH-staining cells in the A1 field. Within the preoptic area, there was reduced (P<0.02) DBH staining in the 16 h EB-treated ewes. There was no change in the DBH staining in the paraventricular nucleus or the arcuate nucleus of the hypothalamus. These data suggest that there is release of noradrenaline in the preoptic area at the time of the E-induced GnRH/LH surge in the OVX ewe.

Animals↗
PubMed1999

Oestrogen receptors in the brainstem of the female sheep: relationship to noradrenergic cells and cells projecting to the medial preoptic area.

Oestrogen regulates the secretion of gonadotropin releasing hormone (GnRH) and this could be mediated by noradrenergic systems originating in the brainstem. Whilst it is known that noradrenergic cells possess oestrogen receptors (ER), it is not known whether ER-immunoreactive (-ir) cells in the brainstem project to the regions of the hypothalamus in which GnRH neurons are found. We have used dual-label immunocytochemistry to determine the extent to which ER-alpha is found in noradrenergic cells in the brainstem of the ovariectomized (OVX) ewe. Noradrenergic/adrenergic cells were identified by immunostaining for dopamine beta-hydroxylase (DBH). Cells that stained for both DBH and ER were found in both the A1 and A2 cell groups, with the highest levels found in the most caudal regions. In the A1 group, at the most caudal extent, 73% of ER-ir cells were DBH-positive and 19% of DBH-ir cells were ER-positive. The degree of co-localization decreased in a linear manner towards the rostral brainstem. In the caudal half of A2, 9-14% of ER-ir cells were DBH-positive and 20-25% of DBH cells were ER-positive. Less than 2% of DBH-ir cells in the A5 group were dual-labelled and none of the cells in the A6 and A7 groups were ER-positive. The retrograde tracer FluoroGold was injected into the preoptic area of nine OVX ewes and labelled cells were examined in the brainstem to determine the extent of co-localization of ER. Only injections in the rostroventral part of the medial preoptic area near to the organum vasculosum of the lamina terminalis resulted in the labelling of cells in the brainstem. One ewe with very strong labelling of the brainstem was selected for detailed mapping. In the ventrolateral medulla, half the ER-ir cells in the most caudal regions were retrogradely labelled. Almost all the ER-ir cells in the mid-region of the ventrolateral medulla were retrogradely labelled but no co-localization of retrograde tracer and ER was observed rostral to obex. There were many ER-ir cells and retrogradely-labelled cells in the nucleus of the solitary tract but only a few double-labelled cells. Similarly, numerous ER-ir cells and retrogradely labelled cells were observed around the lateral edges of the caudal fourth ventricle and across to the lateral parabrachial nucleus but there were few double-labelled cells. These results suggest differential regulation of noradrenergic cells by oestrogen, with a direct action of the hormone confined to the cells in the most caudal region of the A1 and A2 cell groups. The cells of the caudal ventrolateral medulla which contain ER-ir cells that project to the preoptic area may be important in the mediation by noradrenaline of the actions of oestrogen on GnRH secretion in the ewe.

Animals↗