GONADAL-STEROID MODULATION OF NEUROENDOCRINE TRANSDUCTION - A TRANSYNAPTIC VIEW

1. Steroid hormones act on neuronal communication through different me chanisms, ranging from transynaptic modulation of neurotransmitter syn thesis and release to development and remodeling of synaptic circuitry . Due the wide distribution of putative brain targets for steroid horm ones, acute or sustained elevations of their circulating levels may af fect, simultaneously, a variety of neuronal elements. In an elementary mode of interaction, steroids are able to modulate both the synthesis and release of a neurotransmitter at a particular synapse, and the re sponse of its target postsynaptic cells. Using two neuroendocrine tran sducing systems-the rat pineal gland and the GT(1-7) cell line-we have examined these interactions and the following findings are discussed in this article. 2. In the rat, pineal melatonin production is partial ly controlled by gonadal hormones. In females, melatonin synthesis and secretion is reduced during the night of proestrus, apparently as a c onsequence of elevated estradiol and progesterone levels. In males, ci rculating testosterone seems to be necessary to maintain the amplitude of the nocturnal melatonin peak. 3. Some gonadal effects on pineal ac tivity are exerted on its noradrenergic input, since changes in circul ating steroid hormone levels are able to induce acute modifications of tyrosine hydroxylase activity in pineal sympathetic nerve terminals. 4. Gonadal steroids are also able to regulate the response of pineal c ells to adrenergic stimulation, since in vivo treatment of both male a nd female rats with steroid hormone blockers induces profound modifica tions in adrenergically-induced accumulation of cyclic AMP (cAMP) in d ispersed pinealocytes. 5. Direct exposure of pineal cells from gonadec tomized female and male rats to estradiol (E(2)) or testosterone (T), respectively, potentiates pinealocyte response to adrenergic activatio n. In addition, short-term (15 min) exposure to either progesterone (P g) or progesterone coupled to bovine serum albumin (P-3-BSA) suppresse s the E(2)-dependent potentiation of adrenergic response in female rat pinealocytes. 6. Exposure of GT(1-7) cells to E(2) completely blocked the norepinephrine (NE)-induced elevation of cAMP content. In E(2)-tr eated GT(1-7) cells, additional exposure (15 min) to either Pg or P-3- 13SA abolished E(2)-dependent inhibition of NE responsiveness. In addi tion, P-3-BSA alone increased basal cAMP levels in GT(1-7) cells, rega rdless previous exposure to E(2). 7. In conclusion, there are evidence s, both from the current literature and from the present results, supp orting the view that in some neuroendocrine systems gonadal hormones m odulate neurotransmission by acting, simultaneously, at pre- and posts ynaptic sites. The models presented here constitute appropriate exampl es of this transynaptic mode of steroid action and, therefore, may off er a useful approach to investigate steroid hormone actions on the bra in.