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Y. Takei
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K. Ando
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M. Kawakami
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ABSTRACT

A highly specific and sensitive radioimmunoassay has been developed for the measurement of eel atrial natriuretic peptide (ANP). The antiserum, raised against eel ANP-(1–27) did not cross-react with two other eel natriuretic peptides, i.e. eel ventricular natriuretic peptide and C-type natriuretic peptide (CNP), or with any mammalian ANPs, CNPs or brain natriuretic peptides so far identified. The minimal detectable amount was 0·39 fmol (0·90 pg)/tube with more than 99% confidence. Because of its high sensitivity, the radioimmunoassay makes it possible to measure eel ANP directly with only a few microlitres of plasma without extraction.

Using the radioimmunoassay we found high levels of ANP in the atrium (11 ± 2 pmol/mg wet tissue, n = 8), and much lower levels in the ventricle (56 ±8 fmol/mg, n=8) and the brain (22±1 fmol/mg, n = 8) of eels. Eel plasma contained a large amount of ANP (247 ± 66 fmol/ml, n= 8) compared with the levels reported in mammals, although atrial levels are similar between eels and mammals.

Gel-permeation chromography revealed that a major form of ANP stored in the eel atrium, ventricle and brain has a molecular mass of approximately 14 kDa but low molecular forms of about 3 kDa are predominant in eel plasma. A detailed analysis with reverse-phase high-performance liquid chromatography showed that a major molecular form circulating in eel plasma is ANP-(1–27). ANP-(1–27) was also detected in small amounts in the eel atrium, ventricle and brain.

Journal of Endocrinology (1992) 135, 325–331

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H. Al-Khouri
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B. D. Greenstein
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ABSTRACT

Cytosols were incubated from the hypothalamus and mid-brain and from the uterus, and incubated with [3H]progesterone alone or in the presence of excess radioinert steroid to reveal saturable binding sites. Bound and free hormone were separated by gel filtration. Scatchard analysis of the binding sites yielded evidence for only one class of binding sites of high affinity and limited capacity. The binding components in the hypothalamus and uterus appeared to fluctuate during the oestrous cycle, attaining a nadir at metoestrus, while those in the mid-brain were apparently unchanged. During pregnancy hypothalamic [3H]progesterone-binding sites appeared to lose affinity for the steroid while in the uterus the affinity for the steroid was unchanged but the absolute numbers of binding sites were greatly increased at day 10. It is concluded, both from studies of the properties intrinsic to the binding reaction and from endocrine correlates, that the macromolecular progesterone-binding components in the brain may be receptors for the hormone and that there may be differences between the properties of progesterone receptors in different tissues. Furthermore, during pregnancy there may be qualitative changes in the neural progesterone receptors which are not mediated by oestradiol.

J. Endocr. (1985) 107, 159–162

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IM Evans
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MR Pickard
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AK Sinha
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AJ Leonard
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DC Sampson
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RP Ekins
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Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

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Nicola A Dennis Department of Anatomy, Department of Surgery, Otago School of Medical Sciences, Brain Health Research Centre

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Gregory T Jones Department of Anatomy, Department of Surgery, Otago School of Medical Sciences, Brain Health Research Centre

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Yih Harng Chong Department of Anatomy, Department of Surgery, Otago School of Medical Sciences, Brain Health Research Centre

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Andre M van Rij Department of Anatomy, Department of Surgery, Otago School of Medical Sciences, Brain Health Research Centre

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Ian S McLennan Department of Anatomy, Department of Surgery, Otago School of Medical Sciences, Brain Health Research Centre

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) Wang PY Protheroe A Clarkson AN Imhoff F Koishi K McLennan IS 2009 Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior . PNAS 106 7203 – 7208 . ( doi:10.1073/pnas.0902253106 ) Wittmann W

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J. S. TINDAL
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G. S. KNAGGS
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A. TURVEY
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SUMMARY

The afferent path of the milk-ejection reflex has been studied in the brain of the lactating guinea-pig in light pentobarbitone anaesthesia. Square-wave pulses were applied between an indifferent electrode in the scalp and a monopolar electrode inserted stereotaxically in the brain. The brain was transected at the mid-cerebellar level to eliminate activation of the sympathetico-adrenal system, and milk-ejection pressure was monitored to detect release of neurohypophysial hormone(s).

The afferent path of the reflex in the caudal midbrain was very compact and lay in the lateral tegmentum. More rostrally, milk-ejection responses were obtained from the tectum and mesencephalic central grey, but the major pathway remained in the lateral tegmentum and passed forward to lie ventromedial to the medial geniculate body, after which it divided into two components which we have termed the dorsal and ventral paths.

The dorsal path traversed dorsomedially across the brainstem to reach the parafascicular thalamic nucleus, the extreme rostral central grey and the periventricular region at the meso-diencephalic boundary, and then continued forward to reach the pituitary stalk and the medial and dorsal hypothalamus. The ventral path traversed ventromedially to enter the subthalamus and then the lateral hypothalamus, in which it passed both to the rostral basal diencephalon and to the pituitary stalk.

In the diencephalon, milk-ejection responses were obtained after stimulation of part of the ventral thalamus, the lateral, dorsal and anterior hypothalamic areas, the dorsomedial, ventromedial, arcuate, supraoptic and paraventricular nuclei, and the pituitary stalk.

It is suggested from these findings that in the guinea-pig the suckling stimulus ascends by the spinothalamic system, and continues rostrally to relay with the medial and ventral thalamus, the dorsal longitudinal fasciculus and the medial forebrain bundle. Other ascending pathways in the medial lemniscus and mammillary peduncle may also be involved, but appear to be of only minor significance.

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M. C. Ruiz de Elvira
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A. K. Sinha
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M. Pickard
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M. Ballabio
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M. Hubank
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R. P. Ekins
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ABSTRACT

Calmodulin-regulated phosphatase activity was measured in the brain of 2-month-old rats born from hypothyroid and normal dams, using a fluorometric enzyme assay developed for this purpose. Calmodulin content was measured in the same brain regions by radioimmunoassay. Significant differences between groups in weight and protein content, basal phosphatase and calmodulin-regulated phosphatase activity were found. The brain region most affected was the cerebellum, where basal and calmodulin-regulated phosphatase activities, and protein content were increased. The data point towards a lasting effect of maternal hypothyroxinaemia on the brain function of the progeny.

Journal of Endocrinology (1989) 121, 331–335

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OC Meijer
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AM Karssen
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ER de Kloet
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The biological mechanisms that determine cell-specific responses to glucocorticoid hormones may overlap with those that are associated with acquired glucocorticoid resistance. Cell and tIssue specificity can be brought about in many different ways. Studies on the brain, an important glucocorticoid target tIssue, may provide examples of regulatory mechanisms underlying response specificity at multiple levels. In this commentary a number of such mechanisms are discussed, with emphasis on regulation of glucocorticoid bio-availability by the efflux transporter P-glycoprotein and on the variable presence of nuclear proteins which modulate or interfere with gluco- and mineralocorticoid receptor-mediated transcription.

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C. P. PHELPS
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J. H. LEATHEM
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SUMMARY

Some developmental and functional manifestations of thyroxine (T4) administered on the first 2 days of postnatal life were studied in the female rat. Brain myelinogenesis estimated by brain esterified cholesterol concentration, and brain myelin age estimated by brain total cholesterol concentration, were subsequently determined. Thyroxine treatment resulted in a greater concentration of esterified cholesterol in the brain than saline treatment, but the latter appeared to delay the normal increase shown by non-injected controls. Thyroxine treatment resulted in total and free cholesterol levels similar to those of non-injected controls, these again being greater than those in saline-treated rats. Cholesterol concentrations in liver and serum were not affected by T4 or saline treatment.

Administration of T4 to female rats before administration of 1·25 mg testosterone propionate on day 7 resulted in an ovarian and uterine weight response to human chorionic gonadotrophin (HCG, 1 i.u./day on days 23–26) on day 27 that was greater than that in litter-mates given saline at birth before testosterone propionate and HCG treatment. Postnatal T4 treatment alone in the female was also associated with a reduced thyroid and pituitary gland enlargement after 7 days of propylthiouracil feeding (0·015% in tap water, days 24–31 of life) when compared with either saline or non-injected controls.

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R. Suzuki
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A. Takahashi
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Y. Takei
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ABSTRACT

The presence of a C-type natriuretic peptide (CNP) has been reported in the brain of mammals, birds, amphibians and teleost fishes, mostly as a 22-residue peptide (CNP-22). In the present study, we attempted to isolate natriuretic peptides from an elasmobranch, Triakis scyllia, using a chick rectum-relaxant assay, and different molecular forms of CNP were found in the brain and heart. Only CNP-22 was recovered from the brain, as is the case in other vertebrates. A large amount of prohormone (proCNP or CNP-115) and small amounts of its C-terminal peptides (CNP-38 and CNP-39) were isolated from the atrium and ventricle, however. No CNP-22 was recovered from the heart. Natriuretic peptides other than CNP were not isolated from Triakis heart and brain by the rectumrelaxant assay. The 22 residues at the C-terminal region of proCNP, i.e. CNP-22, were well conserved when Triakis and mammals were compared, although the sequence homology of the N-terminal segment of proCNP was very low. Not only was CNP-22 identical but the N-terminal segments of proCNP were also quite similar when Triakis and another elasmobranch, Scyliorhinus canicula, were compared. These data suggest that, in elasmobranchs, CNP is a primary hormone in the natriuretic peptide family, and also that CNP is processed differently in the brain and heart.

Journal of Endocrinology (1992) 135, 317–323

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J. Balthazart
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M. Schumacher
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ABSTRACT

Testosterone metabolism in the brain and pituitary and cloacal glands of male and female Japanese quail was studied in vitro during sexual maturation (from 1 day to 5 weeks after hatching).

The production of 5α-dihydrotestosterone in the hyperstriatum and cloacal gland and that of androstenedione in the cloacal gland of males was highest at 1 day after hatching, which could be related to the peak of plasma androgens previously demonstrated in neonatal quail. 5β-Reductase activity was very high in the brain, but not the pituitary or cloacal glands of young chicks and decreased markedly, especially in the hypothalamus, during sexual maturation. As 5β-reduced metabolites of testosterone are inactive androgens, it is suggested that the decrease of 5β-reductase activity with age corresponds to a potentiation of the effects of testosterone at the level of the brain.

J. Endocr. (1984) 100, 13–18

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