Ovarian steroid action in the serotonin neural system of macaques

The serotonin neural system plays an important role in cognitive, emotional and endocrine processes. If the ovarian hormones, oestrogen and progesterone, alter serotonin neural transmission, then functional changes in all of these systems would follow. Therefore, information on the effects of oestrogen and progesterone at a molecular level in the serotonin neural system was sought using non-human primates. Serotonin neurons express nuclear oestrogen receptor β (ERβ) and progesterone receptors (PRs) which are gene transcription factors. Within serotonin neurons, the regulation of three genes related to serotonin neurotransmission was examined. The mRNA for tryptophan hydroxylase (TPH), the committal enzyme in serotonin synthesis, increased significantly with oestrogen treatment and remained elevated when progesterone was added to the oestrogen regimen. Serotonin reuptake transporter (SERT) mRNA decreased significantly with oestrogen treatment and addition of progesterone had no further effect. 5-HT_1A autoreceptor mRNA decreased significantly with oestrogen treatment and addition of progesterone caused a further decrease. Little or no regulation of postsynaptic 5-HT_1A, 5-HT_2A or 5-HT_2C receptor mRNAs was observed in hypothalamic target neurons. TPH protein is increased by oestrogen treatment and remains elevated with addition of progesterone in a manner similar to TPH mRNA. Medroxyprogesterone (MPA) blocked the stimulatory effect of oestrogen on TPH protein and tamoxifen reduced TPH protein levels below that observed in spayed monkeys. Together these data indicate that ovarian hormones and their synthetic analogues could modify cognitive and autonomic neural functions by acting on the serotonin neural pathway.