The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females

Abstract

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits 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 concentrations of pituitary hormones were measured at 09.00. Subsequently 200 μg of TRH and 100 μg of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, β-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses. These results suggest that impaired serotonergic neurotransmission plays a role in the lower basal PRL concentrations in obese subjects. They do not provide evidence that a serotonergic defect influences the releasing hormone-induced pituitary hormone release in obesity. Furthermore, the findings indicate that serotonergic neurotransmission inhibits TSH release in response to TRH in both obese and normal subjects.