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S. A. D'ANGELO
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SUMMARY

Experimental analysis of the rat's hypothalamic-hypophysial-thyroid system, utilizing stereotaxic, radiometric, histochemical, and bioassay procedures, indicated that electrolytic lesions in the anterior and tuberal portions of the hypothalamus altered thyrotrophic hormone (TSH) secretion in the adenohypophysis and reduced thyroid function (histology and 131I release from the gland). Inhibition of thyroidal radio-iodine release was found within 2 weeks after hypothalamic destruction and was greater in rats which became obese. Significant reduction in titres of circulating TSH also occurred. TSH concentration in the smaller pituitaries of animals in which lesions had been made remained normal, but total hormonal stores decreased.

Thyroxine and triiodothyronine suppressed markedly and equally TSH secretion in the adenohypophyses of operated and intact rats; triiodothyronine was more potent (about 5:1). Hypothalamic damage did not prevent the re-accumulation of TSH in pituitaries previously depleted of their hormone by propylthiouracil; pituitary TSH concentrations rebounded to supranormal levels, but titres in blood decreased to subnormal values. The physiological and histochemical changes induced in the adenohypophyses of rats with lesions strongly implicated the basophils (β cells) in the genesis of TSH. All anterior pituitary cell types were affected in hypothalamic deficiency, but only the β basophils persisted when TSH stores were high, or disappeared when the pituitary was depleted of TSH with exogenous thyroid hormone.

The experimental results indicated that the hypothalamus modulates the activity of the pituitary-thyroid system by influencing production and release of TSH by the pituitary. Hypothalamic regulation of TSH secretion exists for normal conditions as well as for those situations in which enhanced TSH secretion is required. The maintenance of abundant TSH reserves in the adenohypophysis, their depletion after thyroid hormone, and their re-accumulation after goitrogen withdrawal, nevertheless revealed: (1) that the 'isolated' rat pituitary possesses a good measure of autonomous TSH function; (2) that thyroid hormone can act directly on the adenohypophysis independently of the hypothalamus; and (3) that the basic thyroid-pituitary servomechanism is systemically controlled by circulatory levels of thyroid hormone and is not under neural domination.

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K.-P. Yang
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N. B. Haynes
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G. E. Lamming
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ABSTRACT

Opioid-binding sites were quantified in the ewe hypothalamus using [3H]diprenorphine ([3H]DIP) as the radioligand. [3H]DIP binding to hypothalamic membrane preparations was stereospecific, saturable with respect to [3H]DIP concentration, and linear with hypothalamic membrane protein content. Scatchard analysis revealed a single class of binding sites. There were no significant differences in binding site concentration or binding affinity in hypothalami from intact ewes during the breeding and non-breeding seasons, or from long-term ovariectomized ewes with and without oestradiol treatment during the breeding season. Thus, whilst ovarian steroid hormones are known to modify LH responses to opioids and their antagonists in the ewe in vivo, they do not appear to do this by modulating the numbers of hypothalamic opioid-binding sites.

Journal of Endocrinology (1989) 122, 763–767

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MARIETTA VÉRTES
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R. J. B. KING
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SUMMARY

The uptake of [6,7-3H]oestradiol in vivo and in vitro by cell fractions from regions of rat brain and the anterior pituitary gland has been studied. Cytoplasmic and nuclear receptors were detected in anterior and posterior hypothalamus but not in brain cortex.

After labelling in vivo, tissues took up [6,7-3H]oestradiol in the following order of magnitude: anterior pituitary > anterior hypothalamus > posterior hypothalamus > cortex. With the exception of the cortex, all extracts from mature tissues had a higher uptake/mg protein than did extracts from immature animals. In the in-vitro system, oestradiol-17β competed with [6,7-3H]oestradiol-17β in the hypothalamus whereas progesterone, testosterone and oestradiol-17α did not. In the pituitary, oestradiol-17α and 17β competed for binding sites.

A single injection of testosterone propionate on the second day of life affected [6,7-3H]oestradiol binding in later life. By 28 days of age, the androgenized animals had a lower nuclear and higher cytoplasmic uptake of [6,7-3H]oestradiol in anterior hypothalamus. This effect was not seen in the posterior hypothalamus or cortex. Binding was decreased in all fractions from the pituitary. In mature animals (60 days old), binding fell in both nuclear and cytoplasmic fractions from anterior hypothalamus and pituitary. The nuclei from posterior hypothalamus also took up less [6,7-3H]oestradiol after androgenization. Androgenization affected specific binding in uteri at both 28 and 60 days of age.

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JEAN E. M. BUTLER
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B. T. DONOVAN
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SUMMARY

Under stereotaxic guidance, the connexions between the hypothalamus and the rest of the brain were severed surgically in mature female guinea-pigs, and reproductive function was assessed by following the vaginal cycle and by histological study of the ovaries. Animals in which the hypothalamic island incorporated the suprachiasmatic nuclei, or in which the anterior connexions to the hypothalamus were severed by a cut placed just anterior to the suprachiasmatic nuclei, developed persistent vaginal oestrus. Such an anterior cut in the hypothalamus did not influence luteal function in hysterectomized animals. When the anterior border of a hypothalamic island, or an anterior cut through the hypothalamus, was caudal to the suprachiasmatic nuclei, oestrous cycles continued although they were slightly irregular. The ovaries contained corpora lutea. Severance of the posterior connexions to the hypothalamus did not alter the oestrous cycle. The role of the suprachiasmatic area in the generation of persistent vaginal oestrus is discussed.

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PJ Morgan
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AW Ross
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JG Mercer
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P Barrett
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The photoperiodic mammal undergoes quite remarkable changes in physiology as part of its natural adaptations to seasonal fluctuations in the environment. Changes in energy balance and body weight are among these adaptations. In some seasonal mammals, such as the Siberian hamster (Phodopus sungorus), these changes in body weight have been explored in detail, and there is evidence for tightly controlled systems of energy balance that are coordinated by photoperiod acting via the temporal pattern of melatonin secretion from the pineal gland. The pathways and systems involved appear to be quite distinct from the hypothalamic pathways identified to regulate energy balance in studies of both mice and rats thus far. Instead it appears that in the Siberian hamster a tightly regulated system under the control of photoperiod is able to reset the tone of the systems involved in energy balance regulation. Understanding how photoperiod and melatonin act within the hypothalamus to regulate energy balance offers potentially fundamental and important new insights into the control of energy balance. This review describes the current state of our knowledge.

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Alicia J Klecha Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Ana M Genaro Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Gabriela Gorelik Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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María Laura Barreiro Arcos Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Dafne Magalí Silberman Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Mariano Schuman Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Silvia I Garcia Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Carlos Pirola Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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Graciela A Cremaschi Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 15, Primera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina

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less attention than those from hormones of the hypothalamus–pituitary–adrenal axis ( Dorshkind & Horseman 2000 , Wang & Klein 2001 ). This fact could be related to the dominating role of autoimmunity in the pathogenesis of thyroid disorders

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Mohammad Reza Safarinejad
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Kamran Azma Urology and Nephrology Research Center, Department of Physical Medicine and Rehabilitation, Department of Health and Community Medicine, Shahid Beheshti University (MC), PO Box 19395-1849, Tehran, Iran

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Ali Asgar Kolahi Urology and Nephrology Research Center, Department of Physical Medicine and Rehabilitation, Department of Health and Community Medicine, Shahid Beheshti University (MC), PO Box 19395-1849, Tehran, Iran

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exercise ( Kujala et al . 1990 ). Qualitatively and quantitatively normal spermatogenesis is critically dependent on an intact hypothalamus–pituitary–testis (HPT) axis. Androgens are essential for the maintenance of normal spermatogenesis. Reactive oxygen

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LE Pritchard
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AV Turnbull
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A White
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Bioactive peptides derived from the prohormone, pro-opiomelanocortin (POMC), are generated in neurons of the hypothalamus and act as endogenous ligands for the melanocortin-4 receptor (MC4R), a key molecule underlying appetite control and energy homeostasis. It is therefore important to understand many aspects of POMC gene regulation in the brain, as pharmacological manipulation of POMC expression/processing could be a potential strategy to combat obesity. Most studies that have analysed POMC gene expression in the hypothalamus have focused on gene transcription experiments. Ultimately, however, factors that regulate post-translational processing and secretion of peptides will have most bearing on melanocortin signalling. This article focuses on (a) current evidence that POMC is involved in obesity, (b) how POMC transcription is regulated in the hypothalamus, (c) the mechanism by which proteolytic processing of POMC is controlled in the hypothalamus and what peptides are produced and (d) which POMC-derived peptides are the most potent ligands at the melanocortin receptor in vitro and in vivo. It seems that post-translational cleavage of POMC in the hypothalamus may be regulated with respect to energy requirement. We predict that further research into hypothalamic POMC processing, and the proteolytic enzymes involved, may yield important new clues on how flux through the MC4R pathway is regulated.

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M. WINNICK
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R. O. HUSSA
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T. WINNICK
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SUMMARY

The biosynthetic activity of several bovine tissues was compared in slice incubation experiments based on the incorporation of 3H-labelled amino acids. An approximate parallelism was observed between general protein and peptide synthesis in each case. The highest activity was observed in hypothalamus and median eminence, followed by adeno- and neurohypophysis, while liver cells were least potent in these processes. A radioactive polypeptide preparation, isolated from hypothalamus and median eminence experiments, was found to resemble adrenocorticotrophin in certain physico—chemical properties, including molecular size and pattern of isotopic leucine incorporation.

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Lovisa Lundholm
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Milica Putnik
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Michio Otsuki Department of Biosciences and Nutrition at Novum, Department of Medicine, Division of Endocrinology, Karolinska Institutet, SE-141 57 Huddinge, Sweden

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Sandra Andersson
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Claes Ohlsson Department of Biosciences and Nutrition at Novum, Department of Medicine, Division of Endocrinology, Karolinska Institutet, SE-141 57 Huddinge, Sweden

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Jan-Åke Gustafsson
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Karin Dahlman-Wright
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promoters ( Nilsson et al . 2001 ). ERα is the main ER mRNA expressed in mouse adipose tissue ( Lundholm et al . 2004 ). Both ERα and β mRNAs are expressed in mouse hypothalamus ( Couse & Korach 1999 ). Knockout mouse models have shed light on the role of

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