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We studied osmoregulation of plasma vasopressin (AVP) in eight patients with untreated myxedema due to primary hypothyroidism. All patients had severe thyroid hormone deficiency due to chronic thyroiditis and had been receiving no medication at the time of this study. AVP release was defined by 5% hypertonic saline infusion test in all patients, and urinary diluting capacity was estimated by the iv water-loading tests in five patients. Plasma AVP was measured by sensitive and specific RIA. The mean basal plasma AVP level in the patients (0.5 +/- 0.1 pmol/L) was significantly lower (P less than 0.01) than that in normal adults (2.5 +/- 0.5 pmol/L). During hypertonic saline infusion, the rise in plasma AVP was normal or subnormal in all patients. In two patients who showed mild to moderate hyponatremia in the basal state and mild urinary diluting defect during water loading, plasma AVP was appropriately suppressed in each case. These results indicate that inappropriate elevation of plasma AVP is not common in myxedema, and that impaired water excretion is due mainly to AVP-independent mechanisms.

The effect of U50488H, a potent opioid K-receptor agonist, was investigated on the urine volume and on the secretion of arginine vasopressin (AVP) in response to dehydration or hyperosmolar or hypovolemic stimulation in conscious rats. This agonist markedly increased the urine volume in normally hydrated rats and suppressed plasma AVP in a dose-dependent manner in rats given hyperosmolar saline. This suppression of plasma AVP was completely reversed by concurrent injection of naloxone. U50488H also inhibited the release of AVP in dehydrated or hypovolemic rats. These findings indicate that the diuresis induced by U50488H is mainly caused by the suppression of plasma AVP. They also suggest that the K-opioid receptor plays an important role in regulating the secretion of AVP.

No abstract

Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.

Summary. An in vitro perifusion system was used to study parathyroid hormone (PTH) secretion in response to calcium (Ca) and beta-adrenergic agents. Perifused parathyroid tissue responded to changes in Ca within the physiologic range during experiments up to 5 h. There was rapid secretory stimulation after exposure to low Ca, with the maximum response being observed at 20 min. Normal bovine glands showed a Ca-independent nonsuppressible component of PTH release at concentrations of Ca above physiologic. 1-isoproterenol produced rapid stimulation of PTH release, the response being blocked by a beta antagonist. The maximum secretory response to either low Ca (0.5 mM) or 1-isoproterenol (10 -5 M) was enhanced when the two stimuli were applied simultaneously. The response to isoproterenol was blocked by raising Ca to 2.5 raM. Although d,l-propranolol (10 -4 M) caused mild suppression of PTH release at a Ca of 1.25 raM, it did not cause additional suppression at 2.5 mM Ca nor did it decrease the response to 0.5 mM Ca stimulation. The secretory response of the gland to low Ca was sustained at a level more than double the baseline rate. The response to isoproterenol was more transient, with a return to or toward baseline secretion within 60 rain. These results suggest that beta agonists and low Ca have separate but related mechanisms for stimulating PTH release and may affect different pools of hormone. The perifusion system described is a relatively simple technique for assessing the kinetics and interactions of various stimulators of PTH secretion.

HLA antigen phenotypes and BglII restriction fragment length polymorphism of T cell receptor beta-chain (TCR beta) gene were analyzed in 61 patients with Graves' disease and 50 patients with Hashimoto's thyroiditis. The antigen frequency of HLA-Bw46 in both Graves' disease (23.0%) and Hashimoto's thyroiditis (24.0%) was significantly higher than that in normal population (8.0%), with relative risks (RR) of 3.45 [corrected P (Pc) less than 0.009] and 3.66 (Pc less than 0.02), respectively. Significantly increased frequency of HLA-B51 antigen was also found in Hashimoto's thyroiditis (40.0% vs. 16.3% in controls; RR, 3.42; Pc less than 0.002). Hybridization of BglII-digested DNA with TCR beta probe revealed two alleles of 9.3 and 8.6 kilobases. The allele frequency of 8.6 kilobases in Graves' disease (79%) and Hashimoto's thyroiditis (76%) was significantly higher (P less than 0.01 and P less than 0.05, respectively) than that in controls (64%). The frequency of homozygous state 8.6/8.6 was significantly increased in both Graves' disease (62%) and Hashimoto's thyroiditis (60%) over that in controls (39%); the RR of 8.6/8.6 in Graves' disease and Hashimoto's thyroiditis were 2.55 (P less than 0.01) and 2.31 (P less than 0.05), respectively. These results indicate that in Japanese subjects at least two loci are involved in the susceptibility to Graves' disease and Hashimoto's thyroiditis, one related to HLA and another to TCR beta.

In cloned osteoblast-like cells, MC3T3-E1, 12-O-tetradeeanoylphorbol-13-acetate (TPA), a protein kinase C activating phorbol ester, and I-oleoyl-2-acetylglycerol (OAG), a specific activator for protein kinase C, stimulated DNA synthesis in a dose-dependent manner. Both TPA and OAG acted synergistically with insulin-like growth factor I to stimulate DNA synthesis. TPA as well as OAG suppressed the increase in alkaline phosphatase activity of MC3T3-E 1 cells induced by parathyroid hormone. These results suggest that protein kinase C is involved in the process which directs osteoblastlike cells toward proliferation.Protein kinase C; Osteoblast