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ABSTRACT
Galanin-like immunoreactivity (IR) was measured by radioimmunoassay in extracts of non-tumorous and tumorous human pituitaries and in multiple sites in the human brain. Galanin-IR was present in considerable quantities in the non-tumorous pituitaries (21·4±1·2 pmol/g wet weight; mean ± s.e.m., n = 30). In 25 pituitary tumours, galanin-IR was detectable in extracts of only nine, with a mean concentration of 11·5±4·4 pmol/g. Galanin-IR was undetectable in the remaining 16. Of ten brain sites, galanin-IR was detected only in the hypothalamus, where the concentration was 9·1±1·8 pmol/g (n = 5). On fast protein liquid chromatography of the non-tumorous pituitary extracts, galanin-IR mostly eluted in a peak with a retention time similar to that of synthetic porcine galanin. On gel permeation chromatography, galanin-IR eluted as a peak with an elution coefficient (K av) of 0·72, also similar to that of porcine galanin, with additional preceding (K av 0·62) and following (K av 0·77) peaks of galanin-IR. These results show that healthy human pituitary and hypothalamus contain substantial amounts of galanin, whereas it is present in variable amounts or not at all in pituitary tumours. Chromatographic analysis suggests that pituitary galanin is present in three molecular forms, with the majority corresponding to synthetic porcine galanin.
Journal of Endocrinology (1991) 130, 463–467
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ABSTRACT
To study brain sites involved in the regulation of GH secretion in the domestic fowl, lesions were placed in and around the hypothalamus of 1-week-old cockerels. Circulating concentrations of GH were then measured at weekly intervals for 4 weeks after the placement of lesions. At the termination of the experiment, histological procedures were used to determine the exact site of the lesion in each bird. Although a fair degree of overlap existed between the lesion sites leading to stimulation and those causing an inhibition of GH secretion, a clear distinction could be made in the overall distribution of stimulatory and inhibitory sites of GH control. A high concentration of lesion sites resulting in GH decline (presumed GH-releasing factor-rich areas) appeared to reside in the general area of the ventromedial and the arcuate nucleus of the hypothalamus. Lesion sites causing a GH rise (presumed somatostatin-rich areas), on the other hand, seemed to have a more caudal distribution. In addition, some evidence of an anterior hypothalamic distribution of these presumed 'somatostatin' neurones was observed. These agree with the existing immunohistochemical data on the distribution of somatostatin and constitute experimental evidence for localization of presumed GH-releasing factor sites within the avian brain.
J. Endocr. (1984) 103, 327–332
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This study describes the presence of a population of oestrogen receptors in cell nuclei from the pituitary gland and brain of untreated and oestradiol-treated ovariectomized rats. The receptors behaved as if they were not occupied by oestradiol. These 'unfilled' oestrogen receptors could be distinguished from occupied nuclear receptor sites on the basis of their ability to bind [3H]oestradiol at low temperatures (0–4 °C). Occupied receptors bound labelled [3H]oestradiol only under exchange conditions at an increased temperature (25 °C). Unfilled and occupied nuclear receptors were physicochemically similar in terms of sedimentation coefficients in sucrose density gradients containing 0·4 m-KC1 (4–5S), equilibrium dissociation constants for reaction with [3H]oestradiol (0·2–0·6 nmol/l) and ligand specificity. In ovariectomized rats, unfilled receptors constituted more than 75 % of the total nuclear receptor population. One hour after i.v. treatment with oestradiol (3·6 μg/kg), both total and unfilled nuclear receptor concentrations increased and then subsequently declined over the next 12 h. The increase in unfilled sites was, however, proportionately less than that occurring in the filled component; at 1 h after oestradiol injection unfilled sites constituted less than 20% of the receptors present in brain and pituitary cell nuclei. The physiological significance of unfilled nuclear oestrogen receptors remains unknown. The observations that they exist in various oestrogen target tissues and that their levels are influenced by oestradiol treatment suggest a possible role for these receptors in the mechanism of oestrogen action.
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Glucocorticoids regulate corticotropin-releasing hormone (CRH) gene expression in the placenta and the brain. In both the placenta and two extrahypothalamic sites in the brain (the amygdala and the bed nucleus of the stria terminalis), glucocorticoids elevate CRH gene expression. One functional role of the elevation of CRH by glucocorticoids may be to signal adversity. When CRH is over-expressed in the placenta, it may indicate that the pregnancy is in danger, and preterm labor may result. When CRH is over-expressed in the brains of animals, they may become more fearful. Both situations possibly reflect allostatic mechanisms and vulnerability to allostatic overload, a condition in which biological tissue may be compromised.
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In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of 125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presence of other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.
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SUMMARY
The lateral hypothalamus, and various sites within the limbic system and frontal lobe of the rhesus monkey brain were electrically stimulated using chronically implanted electrodes. A considerable increase in plasma aldosterone levels was observed after stimulation of the lateral hypothalamic area, certain localized sites in the cingulate area, and lower medial parts of the frontal lobe. Inactive sites included most of the amygdala, hippocampus, and basal ganglia, together with other areas within the frontal lobe and cingulate gyrus. Stimulation of all active areas was followed by an increase in plasma renin activity. Plasma cortisol also increased considerably after hypothalamic stimulation but in the case of extra-hypothalamic sites the cortisol response was much less.
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University of Oxford, John Radcliffe Hospital, Department of Obstetrics and Gynaecology, and Nuffield Institute for Medical Research, Headley Way, Headington, Oxford, 0X3 9DU
(Received 29 December 1975)
Although steroid hormones have well recognized effects on the brain and uterus, and their specific uptake in target tissues has been demonstrated (see Baulieu, 1975), there is little information concerning the concentrations of steroids in these areas of the body. In the present study we have compared the concentration of two steroids, progesterone and oestradiol, in neuroendocrine and uterine tissues of ovariectomized sheep treated with physiological amounts of the hormones.
Sixteen sexually mature ewes (Clun Forest or Border Leicester) were bilaterally ovariectomized through a mid-ventral incision during the period of seasonal anoestrus. The animals were divided into four equal groups and received the following hormone injections (i.m., twice daily at 09.00 and 18.00 h for 10 days: Group I, 0·5 ml ethanol (vehicle
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SUMMARY
The development of the pituitary-adrenocortical stress response was studied in CBA/J × DBA/2J hybrid mice. On the basis of the plasma corticosterone response 15 min after a subcutaneous injection of histamine dihydrochloride (50 mg/kg), the first three neonatal weeks could be divided into stress-nonresponsive (3–211 days) and stress-responsive 16–21 days) periods. During the former period, corticosterone levels in the brains of the non-stressed control mice were 63% higher than those of comparable mice during the latter period. Histamine stress significantly increased corticosterone concentrations in the brain during both these periods, but the increase was much greater (88%) during the stress-responsive period than during the stress-nonresponsive period (29%).
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ABSTRACT
The influence of maternal hypothyroxinaemia on early brain and placental development was examined in a partially thyroidectomized (parathyroid-spared; TX) rat dam model. Ornithine decarboxylase (ODC) specific activity, along with more general indices of cell growth, were determined in prenatal whole brain (at 15, 19 and 22 days of gestation), postnatal brain regions (at 5, 10 and 14 days) and placenta.
Maternal hypothyroxinaemia resulted in reductions in fetal body weight, brain weight, brain DNA content and brain total protein content at 15 days of gestation; the latter effect persisting until 19 days of gestation. Further changes in brain cell growth were observed near term, when an increase in the DNA concentration was accompanied by a decrease in the total protein: DNA ratio. Growth of the postnatal brain regions appeared normal, with the exception of an isolated increase in the protein content of the cerebellum at postnatal day 5. Determination of the specific activity of brain ODC revealed a complex pattern of change in the progeny of TX dams, super-imposed upon the normal ontogenetic decline. In the fetal brain, activity was initially deficient at 15 days of gestation but was increased at 22 days of gestation relative to controls. The compromise extended into the postnatal period; ODC specific activity being transiently reduced in the brainstem, the subcortex and the cerebral cortex. Placental development was less consistently affected; wet weight, gross indices of cell growth (DNA content, DNA concentration, total protein: DNA ratio) and ODC specific activity were all normal in the TX dam. However, cytosolic and total protein concentrations were reduced at 15 and 19 days of gestation respectively.
These results demonstrate abnormal fetal brain cell development as a consequence of maternal hypothyroxinaemia. The damage extended into the neonatal period, well after the onset of fetal thyroid hormone synthesis. Although the reduced supply of maternal thyroxine to the fetal brain may play a major role in this dysgenesis, factors such as the impairment of placental function must be taken into consideration.
Journal of Endocrinology (1993) 139, 205–212
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ABSTRACT
Changes in plasma concentrations of sex steroids were examined in male and female zebra finch chicks during the sensitive period for differentiation of sexually dimorphic brain nuclei associated with the control of song. Using a chromatographic separation procedure and radioimmunoassay, androstenedione, testosterone and 5α-dihydrotestosterone were detected in plasma at relatively high concentrations immediately after hatching. There were no sex differences in concentrations of these androgens. An oestrogen, oestradiol-17β, which is known to differentiate the song-control system, is raised specifically in the circulating plasma of male zebra finch chicks, and not in females. The surge in oestradiol, which occurs during the first week after hatching, coincides with the period when capacity for differentiation of the song system is maximal. Exposure of the male brain to oestradiol-17β could trigger neuronal differentiation.
J. Endocr. (1984) 103, 363–369
