THE INFLUENCE OF SEROTONERGIC NEUROTRANSMISSION ON PITUITARY-HORMONE RELEASE IN OBESE AND NONOBESE FEMALES

It has been suggested that a defect in hypothalamic serotonergic neuro transmission may be partly responsible for the impaired pituitary horm one release in obese subjects. In this study we investigated basal ser um pituitary hormone concentrations and pituitary hormone release in r esponse to the sequential injection of four hypothalamic releasing hor mones before and after a seven-day course of fluoxetine, which inhibit s serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI) 35.6 +/- 1.0 kg/m2) and nine women of normal weight (BMI 22.9 +/- 0.9 kg/M2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal c oncentrations of pituitary hormones were measured at 09.00. Subsequent ly 200 mug of TRH and 100 mug of CRH, GnRH and GHRH were injected intr avenously. The pituitary hormone response was measured at regular inte rvals until 180 min after the four injections. The experiment was repe ated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be sign ificantly lower in obese subjects than in the normal controls. Basal c oncentrations of ACTH, beta-endorphin, TSH, LH and FSH in the two grou ps were comparable. Releasing hormone-induced responses in the two gro ups were not significantly different. Administration of fluoxetine ''r estored'' the basal PRL concentrations in obese subjects. It did not a ffect the other basal hormone concentrations. Furthermore. fluoxetine treatment reduced TRH-induced TSH release in both normal and obese sub jects. It did not influence the other releasing hormone-induced respon ses. These results suggest that impaired serotonergic neurotransmissio n plays a rote in the lower basal PRL concentrations in obese subjects . They do not provide evidence that a serotonergic defect influences t he releasing hormone-induced pituitary hormone release in obesity. Fur thermore. the findings indicate that serotonergic neurotransmission in hibits TSH release in response to TRH in both obese and normal subject s.