The role of opiate, dopaminergic, and adrenergic systems in the hypothalamo-pituitary dysfunction in obesity

Abstract

In order to evaluate the role of opiate, dopaminergic and adrenergic systems in the mechanism of hypothalamo-pituitary disturbances in obesity, 9 obese women and 14 healthy women were investigated. Serum GH, LH, \g=b\-endorphin and cortisol concentrations were measured after administration of clonidine, an \g=a\2-adrenergic receptor agonist, and naloxone, an opiate antagonist. Additionally, PRL levels were measured after administration of the dopamine receptor blocker metoclopramide. An impaired GH response to clonidine and naloxone was found in obese women.However, a marked increase in \g=b\-endorphin was observed in obese patients after clonidine administration. Naloxone did not cause any significant change in \ g = b \ \ x = r e q -\ endorphin release. Neither clonidine nor naloxone induced any change in LH release. Serum PRL concentrations in response to metoclopramide were significantly higher in obese patients than in healthy women. In conclusion: Disturbed activity in opiate, adrenergic, and dopaminergic systems may be of pathogenetic importance in a hypothalamo-pituitary dysfunction in obesity. The occurrence of hypothalamic amenorrhoea as well as the presence of abnormalities of the central nervous system regulation of GH, PRL, ACTH, cortisol, insulin and vasopressin output might point to a generalized hypothalamo-pituitary dysfunction in obesity.

Neuroendocrine Abnormalities in Hypothalamic Amenorrhea: Spectrum, Stability, and Response to Neurotransmitter Modulation1

“…Previous work in normally menstruating women demonstrated a decrease in LH secretion after norepinephrine suppression with clonidine (15,16), and the HA subjects in our study also responded to clonidine administration with a significant decrease in mean LH. The finding that clonidine lowered mean LH in our subjects may imply that norepinephrine stimulates LH release in humans as it does in lower mammals.…”

“…Clonidine (Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT), an alpha-2 agonist that reduces central adrenergic output via an autoinhibitory feedback loop on norepinephrine-secreting cells, was administered as a single 0.15 mg oral dose. The dose of clonidine was chosen as that effective to stimulate GH secretion (22,23) and to effectively suppress LH secretion in humans (15,16).…”

“…Although one cannot directly study the impact of opioid tone on hypothalamic GnRH release, the observation that LH pulse frequency (7,8) and amplitude (9) increase after opiate receptor blockade, suggests that an increase in opioid tone may contribute to HA in a subset of women. Other work in humans has explored the role of inhibition by the dopaminergic (10 -15) and noradrenergic systems (7,15,16) with conflicting results.An important question is whether patterns of hypothalamic GnRH secretion vary over time in women, and whether underlying pulse patterns affect clinical presentation or response to neurotransmitters. Previous studies exploring the…”

The effect of clonidine on hormone release mediated through activation of opiate receptors

“…Our results show that clonidine did not change ~-endorphin levels, and the combined therapy of clonidine plus naloxone did not alter i3-endorphin release in healthy women. Our previous studies have demonstrated a marked increase of ~-endorphin release in response to clonidine in obese subjects [2]. We have suggested that alpha2-adrenergic receptor activity may be increased in obesity.…”

Purpose in life (ikigai) may improve obesity caused by stress: a proposal based on traits of neurotransmitters related to emotions

“…People with anxiety attempt to search for pleasure and comfort. Eating [9,10] and drinking alcohol [11] cause temporary pleasure and comfort because neurotransmitters related to pleasure and comfort are secreted [9][10][11]. Additionally, drinking alcohol increases appetite resulting in increasing food intake [12][13][14].…”