Diisopropylfluorophosphate (DFP) reduces serum prolactin, thyrotropin, luteinizing hormone, and growth hormone and increases adrenocorticotropin and corticosterone in rats: Involvement of dopaminergic and somatostatinergic as well as cholinergic pathways

Cholinergic mechanisms have been implicated in the regulation of anterior pituitary hormone secretion. The present study was designed to determine the effect of a single injection of an organophosphate acetylcholinesterase inhibitor, diisopropylfluorophosphate (DFP), on anterior pituitary function in male rats. DFP increased serum ACTH (2.7-fold) and corticosterone (9.1-fold), while suppressing TSH, PRL, LH, and GH by up to 95%. The earliest response was at 1 hr, with a duration of at least 18 hr for TSH and LH. Responses were similar in adrenalectomized animals. After DFP, responses to hypothalamic releasing factors were normal for TSH, GH, and ACTH, but significantly blunted for PRL and LH. TSH suppression was partially prevented by combined therapy with a nicotinic (mecamylamine) and a muscarinic (atropine) antagonist. TSH suppression was partially reversed by immunoneutralization with somatostatin antibody, and PRL suppression was completely prevented by a dopamine antagonist (haloperidol). Atropine alone prevented the effects on corticosterone. TSH pituitary content and TSH-β mRNA were reduced by 37 and 22%, respectively, by DFP. In contrast, PRL mRNA was unchanged but PRL content was increased 3-fold. We conclude that cholinesterase inhibition evokes a multiplicity of effects on anterior pituitary function. There is a hierarchy of responses, with corticosterone being the most and TSH the least sensitive. There is evidence for inhibition at both the hypothalamic and pituitary levels, involving both nicotinic and muscarinic receptors. Although cholinesterase inhibition is the proximate event, other neurotransmitter pathways involved in TSH and PRL suppression are somatostatin and dopamine, respectively.