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To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its alpha-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas beta-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. L-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH. Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, alpha-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its alpha-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour. It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.

To clarify the role of blood volume and osmolality in the mediation of the release of atrial natriuretic peptide (ANP) and to examine the relationship between plasma ANP and plasma AVP levels in man, the effects of hypertonic saline and hypertonic mannitol infusion, and of water load on plasma levels of ANP and AVP were studied. Infusion of 5% saline to 7 healthy men at a rate of 0.05 ml.min-1.kg-1 for 2 h resulted in a parallel rise in plasma sodium, osmolality, plasma ANP and plasma AVP, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Infusion of 20% mannitol to 6 healthy men at the same rate resulted in a parallel increase in plasma osmolality, plasma ANP and AVP, whereas plasma sodium decreased, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Water load (20 ml/kg) into 7 healthy men produced a prompt and parallel fall in plasma sodium, plasma osmolality and plasma AVP. In contrast, plasma ANP and plasma volume, calculated from the changes in hematocrit, increased concomitantly, which indicates that expanded plasma volume stimulates secretion of plasma ANP. These results suggest that secretion of ANP in man is regulated principally by plasma volume, which may be modulated by a change in plasma osmolality. AVP secretion, on the other hand, is controlled mainly by osmotic change and secondarily by plasma volume.

The effect of GnRH-associated peptide on PRL secretion by human pituitary lactotropes in culture was studied. Pituitary adenomas obtained at selective transsphenoidal adenomectomy from a patient with prolactinoma, and two patients with mixed GH- and PRL-secreting pituitary adenomas were cultured in monolayer. When cells were incubated with dopamine (10 nmol/l), a significant inhibition in PRL secretion was observed in all the experiments, which was blocked by co-incubation with haloperidol. In mixed GH- and PRL-secreting adenoma cells, dopamine likewise decreased GH secretion. Incubation of cells with synthetic GnRH-associated peptide at concentrations up to 100 nmol/l, on the other hand, failed to affect both PRL and GH secretion. These results suggest that synthetic GnRH-associated peptide has no inhibitory effect on PRL secretion in human pituitary lactotropes.

Serum dehydroepiandrosterone sulphate concentrations were measured in 70 patients with prolactinoma and in 54 patients with acromegaly with normal adrenocortical function. Compared with values in normal subjects of corresponding age, serum dehydroepiandrosterone sulphate levels were increased in 22 patients with prolactinoma (31%) and in 5 patients with acromegaly (9%). The four acromegalic patients who had elevated serum dehydroepiandrosterone sulphate levels had hyperprolactinemia. The mean serum dehydroepiandrosterone sulphate concentrations in patients with prolactinoma in each decade decreased with advancing age. There was a significant negative correlation between serum dehydroepiandrosterone sulphate concentrations and ages of the patients with prolactinoma. In all 8 women with prolactinoma as in 6 normal women, serum dehydroepiandrosterone sulphate levels declined definitely during the 9 years of follow-up despite persistent hyperprolactinemia. These results indicate that serum dehydroepiandrosterone sulphate levels are increased in a substantial number of patients with hyperprolactinemia, however, PRL per se may not play a significant role in the age-related change in serum dehydroepiandrosterone sulphate levels.