23 February 2001
Nocturnal rise in pineal melatonin output is due to the night-induced acceleration of noradrenergic transmission and α<sub>1</sub>- and β-adrenoceptor activation. In addition, in female animals, cyclic oscillations in circulating levels of sex steroid hormones are accompanied by changes in the rate of pineal melatonin secretion. To investigate whether estrogen directly affects pineal adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats were exposed to physiological concentrations of 17β-estradiol (17β-E<sub>2</sub>) and treated with noradrenergic agonists. Direct exposure to 17β-E<sub>2</sub> reduced α<sub>1</sub>/β-adrenoceptor-induced stimulation of melatonin synthesis and release. This effect was mediated by an estrogen-dependent inhibition of both β-adrenoceptor-induced accumulation of cAMP and α<sub>1</sub>-adrenoceptor-induced phosphoinositide hydrolysis. Furthermore, estrogen reduced transient Ca<sup>2+</sup> signals elicited in single pinealocytes by α<sub>1</sub>-adrenoceptor activation or by potassium-induced depolarization. In the case of β-adrenoceptor responsiveness, neither forskolin- nor cholera toxin-induced accumulation of cAMP were affected by previous exposure to 17β-E<sub>2</sub>. This indicates that estrogen effects must be exerted upstream from adenylylcyclase activation, and independent of modifications in G protein expression, therefore suggesting changes in either adrenoceptor expression or receptor-effector coupling mechanisms. Since estrogen effects upon adrenoceptor responsiveness in pineal cells was not mimicked by 17β-E<sub>2</sub> coupled to bovine serum albumin and showed a latency of 48 h, this effect could be compatible with a genomic action mechanism. This is also consistent with the presence of two estrogen receptor proteins, α- and β-subtypes, in female rat pinealocytes under the present experimental conditions.