Abstract:Recently, erythropoietin (EPO) receptors and synthesis of EPO have been identified in the brain. To clarify the effects of EPO on neuronal cells, we investigated the effects of EPO on Ca 2ϩ uptake, intracellular Ca 2ϩ concentration, membrane potential, cell survival, release and biosynthesis of dopamine, and nitric oxide (NO) production in differentiated PC12 cells, which possess EPO receptors. EPO (10 Ϫ12 -10 Ϫ10 M) increased 45 Ca 2ϩ uptake and intracellular Ca 2ϩ concentration in PC12 cells in a dose-related manner; these increases were inhibited by nicardipine (1 M) or anti-EPO antibody (1:100 dilution). EPO induced membrane depolarization in PC12 cells. After a 5-day culture without serum and nerve growth factor (NGF), viable cell number decreased to 50% of that of the control cells cultured with serum and NGF. EPO (10 Ϫ13 -10 Ϫ10 M) increased the number of viable cells cultured without serum and NGF; this increase was blunted by nicardipine or anti-EPO antibody. Incubation with EPO (10 Ϫ13 -10 Ϫ10 M) stimulated mitogen-activated protein kinase activity in PC12 cells. EPO (10 Ϫ13 -10 Ϫ10 M) increased dopamine release from PC12 cells and tyrosine hydroxylase activity; these increases were sensitive to nicardipine or anti-EPO antibody. Following a 4-h incubation with EPO (10 Ϫ14 -10 Ϫ10 M), NO production was increased, which was blunted by nicardipine and anti-EPO antibody. In contrast, maximal NO synthase activity was not changed by EPO. These results suggest that EPO stimulates neuronal function and viability via activation of Ca 2ϩ channels. Key Words: Erythropoietin-PC12 cells-Ca 2ϩ channels-Cell survivalDopamine release -Nitric oxide.

Objective: Several reports have described antipituitary antibodies by immunofluorescent or immunoblotting methods in patients with lymphocytic hypophysitis. However, with the exception of the pituitary hormones, individual antigens specific for the pituitary gland have not been studied. To understand the pathogenesis of lymphocytic hypophysitis and to diagnose this disease efficiently, we studied the presence of autoantibodies against three pituitary-specific proteins, GH and two novel pituitary-specific proteins, namely, pituitary gland specific factor 1a (PGSF1a) and PGSF2. Design: Seventeen patients with lymphocytic hypophysitis, all of whom had pituitary enlargement (5 with lymphocytic adenohypophysitis and 12 with lymphocytic infundibuloneurohypophysitis, including 3 of the latter group proven by biopsy), and 14 patients with hypopituitarism without pituitary enlargement (10 with isolated ACTH deficiency and 4 with idiopathic TSH deficiency) were studied, and compared with 11 patients with non-functioning pituitary macroadenoma, 31 patients with other autoimmune diseases, and 36 healthy controls. Methods: The presence of each antibody was studied by radioligand assay using recombinant human 35 S-labeled protein.Results: Three (18%) patients with lymphocytic hypophysitis having pituitary enlargement, five (36%) patients with hypopituitarism without pituitary enlargement and three (9.7%) patients with other autoimmune diseases were positive for one or more of the antibodies studied. Conclusions: Anti-human GH, anti-PGSF1a, and anti-PGSF2 antibodies were detected in patients with lymphocytic hypophysitis and other hypopituitarism, but were not detected in patients with non-functioning pituitary macroadenoma. Detection of these antibodies may be useful for the diagnosis of lymphocytic hypophysitis.

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Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GHreleasing hormone (GHRH), somatostatin (SRIF), GHreleasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GHsecretion are neural endogenousrhythm, sleep, stress, exercise, and nutritional and metabolic signals. GHdeficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GHdeficiency can be treated with recombinant humanGH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GHhypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GHcan be treated by transshenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GHsecretion in combination with or without the surgery. (Internal Medicine 41: 7-13, 2002)

Butylation problems ironed out: 3‐Pentynyl ethers react with butyllithium at −20°C in toluene, upon addition of a catalytic amount of a cheap iron(III) salt, to afford (E)‐4‐methyl‐3‐octenyl ethers in high yields. Stereochemically defined tetrasubstituted alkenes were also obtained by the subsequent addition of electrophiles (E+, see scheme; acac = acetylacetonate, Bn=benzyl).