E. del Pozo

EFFECT OF BROMOCRIPTIN ON THE ENDOCRINE SYSTEM AND FETAL DEVELOPMENT

A preliminary report on the endocrine effects of bromocriptin (CB 154) on pituitary hormones has already been published (del Pozo et al., 1973). In the mean time these studies have been extended to consider other endocrine parameters. This paper illustrates the effect of acute and chronic treatment with bromocriptin on growth hormone (hGH), placental Iactogen (hPL), thyro trophin (TSH), insulin (IRI), cortisol, aldosterone, and free fatty acids (FFA). In addition, observations on the action of bromocriptin on pregnancy and fetal development are presented.

Effect of a Long-Acting Somatostatin Derivative SMS 201-995 (Sandostatin) on Glucose Homeostasis in Type I Diabetes mellitus

The infusion of natural somatostatin (SRIF) has been able to partially correct postprandial hyperglycemic reactions in insulin-dependent diabetes mellitus (IDDM). SMS 201-995 (Sandostatin) is a long-acting derivative with a growth hormone-suppressive effect 10-60 times more potent than the native peptide. The effect of SMS 201-995 (50 micrograms s.c.) on glucose control by exogenous insulin has been documented in a series of type I diabetics after stabilization of blood sugar by an artificial pancreas. Inhibition of counterregulatory mechanisms significantly diminished the postprandial hyperglycemia, and insulin requirements, both total and 2 h after meals, were markedly decreased. Also the effect of a single s.c. injection of 100 micrograms SMS 201-995 on the dawn phenomenon in a patient with poorly adjustable diabetes was investigated. The glucose escape observed during the control night was blocked by SMS 201-995. Thus, the stabilizing action of this peptide on postprandial and nocturnal hyperglycemia in unstable diabetes warrants further studies.

Effect of two serotonin antagonists on prolactin release induced by breast stimulation in postpartum women.

The possible role of serotonin on prolactin (PRL) secretion was investigated by measuring PRL plasma levels before and after mechanical breast stimulation in puerperal women. Two serotonin antagonists

CHRONIC DOPAMINE RECEPTOR STIMULATION USING BROMOCRIPTINE: FAILURE TO MODIFY THYROID FUNCTION

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 μg TRH, but significantly (P < 0.01) blunted it after 200 μg. Chronic bromocriptine treatment (7.5–50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 μg TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.

Size Changes of a Growth Hormone- and Prolactin-Producing Adenoma during and after Sandostatin Treatment

A 46-year-old woman with acromegaly and marked hyperprolactinemia was treated chronically with sandostatin (50 micrograms b.i.d. up to 100 micrograms t.i.d.). Plasma growth hormone (GH) was reduced by 90% of basal values and prolactin (PRL) dropped from initially 204 to 74 ng/ml. Serial CAT scans detected a volume reduction of the pituitary adenoma of 46.7%, but discontinuation of therapy was followed by re-expansion of the tumor. Tissue collected at transsphenoidal adenomectomy was examined by immunohistology and found positive for both GH and PRL. This characteristic would explain the dual hormonal response to the specific GH inhibitor sandostatin.

Management of borderline hyperprolactinemia.

Progressively increasing plasma prolactin (PRL) concentrations are currently associated with menstrual disturbances, anovulation and cessation of cyclic activity. Galactorrhea-amenorrhea in the presen

Long-Term Systemic Administration of Human Recombinant Interleukin-1β Induces a Dose-Dependent Fall in Circulating Parathyroid Hormone in Rats

The synergism/antagonism between interleukin (IL)-1β and parathyroid hormone (PTH) has been the subject of in vitro and in vivo work, but a possible direct action of the cytokine on PTH release has not been reported. We have investigated the effect of a continuous infusion of human recombinant IL-1β (rIL-1β) on circulating PTH during a 14-day period in 7-week-old female rats. This time interval was chosen in order to exclude initial hypercalcemia and to enable data collection under steady-state conditions. Five groups of 20 animals each had miniosmotic pumps (Alzet 2002, 200 µl) implanted subcutaneously and primed to release either distilled water (controls) or 100, 500, 1,000 and 2,000 ng/24 h of rIL-1β. Blood was drawn on days 1 and 14 for PTH, corticosterone and Ca2+ determinations. Adequate biological activity of the infused rIL-1β was supported by elevated rectal temperature records and significant elevations of plasma corticosterone on day 14. The 100-ng dose had no effect but 500–2,000 ng rIL-1β/24 h significantly reduced plasma PTH in a dose-dependent manner down to 54% of basal value (20.4 ± 1.1 vs. 15.3 ± 1.4 pg/ml for 500 ng, p < 0.005; 20.5 ± 1.3 vs 12.3 ± 1.1 for 1,000 ng, p < 0.001, and 19.5 ± 2.0 vs. 10.6 ± 1.1 pg/ml for 2,000 ng, p < 0.0008). Despite these findings, no differences in blood Ca2+ could be detected between treated animals and controls. The following conclusions can be inferred from the foregoing: Systemic administration of rIL-1β to rats induced a dose-dependent fall in circulating PTH without altering calcemia, calling into question the biological relevance of the former finding. Although the recorded PTH depression may indeed not have been severe enough to cause hypocalcemia, it can be hypothesized that osteoclast activation by rIL-1β would enhance bone mineral release into the pool compensating for depressed PTH activity.