The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Interleukin-18 (IL-18) has recently been considered a promising marker of stress responses. In this study, to evaluate IL-18 as a noninvasive stress marker in pigs, we investigated the expression of IL-18 in porcine salivary glands and its presence in saliva, and its dynamics during acute immobilization stress in pigs. IL-18 mRNA was detected robustly in the pig salivary glands by RT-PCR. Immunohistochemical staining of IL-18 protein expression revealed that the expression patterns differed among the three types of salivary glands (parotid, submandibular, and sublingual gland). IL-18 was also detected in pig saliva by ELISA, and a diurnal rhythm with a peak in the afternoon was observed. The IL-18 concentration in saliva was significantly increased during a 60-min acute immobilization stress in thirteen 5-month-old pigs. These results are the first evidence of a stress-related change of IL-18 in pig saliva. Salivary IL-18 may thus become a useful noninvasive marker for the evaluation of acute stress in pigs.

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The effect of estrogen on prolactin (PRL) synthesis at a single-cell level was studied by in situ hybridization and immunohistochemistry. Long-term estrogen treatment increased PRL-containing cells from 10–20% of total cell population to 80–90%, as revealed by immunohistochemistry. PRL mRNA containing cells also increased in a similar fashion. Moreover, cytoplasmic PRL mRNA expressed as the number of silver grains per cell increased 4- to 5-fold by estrogen. These results suggest that long-term estrogen treatment causes not only PRL cell proliferation but also an increase in PRL mRNA in a single cell.

It has been reported that the plasma growth hormone (GH) and prolactin (PRL) levels in acromegalic patients were suppressed after intensive administration of dopaminergic drugs, but we found that the plasma GH levels in some acromegalic patients were not suppressed. Plasma GH and PRL levels after a single oral administration of CB-154 (2.5mg) and L-DOPA (1g) were measured in 18 active acromegalic patients with and without galactorrhea. 1. The mean plasma GH levels after the administration were clearly suppressed in 8 patients with galactorrhea, while they were not suppressed in 10 patients without galactorrhea. These drugs were more effective in suppressing plasma GH levels in acromegalic patients with galactorrhea and hyperprolactinemia. 2. We calculated the responsiveness of the plasma GH level as follows: GH responsiveness (%) = (mean plasma GH level after the administration of CB-154 or L-DOPA)/ (basal GH level) x 100. The basal plasma PRL levels were inversely correlated with GH responsiveness (CB-154: r=-0.690, p less than 0.01. L-DOPA: r=-0.541, p less than 0.05). It was found that the effect of dopaminergic drugs on plasma GH levels was closely correlated with basal PRL levels in acromegalic patients. This implies that the chronic administration of CB-154 may be effective in acromegalic patients with galactorrhea and hyperprolactinemia.