La glándula pineal como transductor neuroendocrino / Pineal gland as a neuroendocrine transductors

La glándula pineal de los mamíferos funciona como una interfase neuroendocrina, transformando los cambios de luz ambiental en un mensaje hormonal: la síntesis y liberación nocturna de melatonina. La noradrenalina, liberada desde las terminaciones nerviosas simpáticas procedentes del ganglio cervical superior, interactúa con los receptores - y 1-noradrenérgicos situados en la membrana del pinealocito, iniciando una serie de acontecimientos que culminan en la síntesis de melatonina. La estimulación del receptor activa la adenilato ciclasa, produciendo un rápido incremento en los valores intracelulares de adenosín monofosfato complementario (AMPc), la activación de una proteína cinasa dependiente de AMPc y la fosforilación del factor de transcripción CREB. La interacción del CREB fosforilado con las secuencias específicas en el ADN induce la expresión de la serotonina N-acetil transferasa (SNAT), enzima que cataliza el paso limitante en la síntesis de melatonina. El CREB fosforilado también activa la expresión de una proteína represora que bloquea la transcripción de la SNAT. El receptor 1 potencia la respuesta noradrenérgica activando una proteína cinasa dependiente de Ca+2 y de la hidrólisis de fosfatidilinositol. Además del control nervioso, se ha demostrado que la biosíntesis de melatonina se ve afectada por las oscilaciones de los valores circulantes de esteroides gonadales. En células pineales, las hormonas sexuales regulan directamente la respuesta a la estimulación adrenérgica y, de forma recíproca, la noradrenalina regula la cinética del receptor de estrógenos. En otras áreas del sistema nervioso se han descrito interacciones similares entre hormonas y neurotransmisores, lo que podría representar un mecanismo básico en los procesos de integración neuroendocrina a escala celular. La glándula pineal constituye un modelo extremadamente útil para la disección de los componentes de tales mecanismos (AU)

Gonadal steroid modulation of neuroendocrine transduction: a transynaptic view.

1. Steroid hormones act on neuronal communication through different mechanisms, ranging from transynaptic modulation of neurotransmitter synthesis and release to development and remodeling of synaptic circuitry. Due the wide distribution of putative brain targets for steroid hormones, acute or sustained elevations of their circulating levels may affect, 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 response of its target postsynaptic cells. Using two neuroendocrine transducing systems-the rat pineal gland and the GT1-7 cell line-we have examined these interactions and the following findings are discussed in this article. 2. In the rat, pineal melatonin production is partially controlled by gonadal hormones. In females, melatonin synthesis and secretion is reduced during the night of proestrus, apparently as a consequence of elevated estradiol and progesterone levels. In males, circulating testosterone seems to be necessary to maintain the amplitude of the nocturnal melatonin peak. 3. Some gonadal effects on pineal activity are exerted on its noradrenergic input, since changes in circulating 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 cells to adrenergic stimulation, since in vivo treatment of both male and female rats with steroid hormone blockers induces profound modifications in adrenergically-induced accumulation of cyclic AMP (cAMP) in dispersed pinealocytes. 5. Direct exposure of pineal cells from gonadectomized female and male rats to estradiol (E2) or testosterone (T), respectively, potentiates pinealocyte response to adrenergic activation. In addition, short-term (15 min) exposure to either progesterone (Pg) or progesterone coupled to bovine serum albumin (P-3-BSA) suppresses the E2-dependent potentiation of adrenergic response in female rat pinealocytes. 6. Exposure of GT1-7 cells to E2 completely blocked the norepinephrine (NE)-induced elevation of cAMP content. In E2-treated GT1-7 cells, additional exposure (15 min) to either Pg or P-3-BSA abolished E2-dependent inhibition of NE responsiveness. In addition, P-3-BSA alone increased basal cAMP levels in GT1-7 cells, regardless previous exposure to E2. 7. In conclusion, there are evidences, both from the current literature and from the present results, supporting the view that in some neuroendocrine systems gonadal hormones modulate neurotransmission by acting, simultaneously, at pre- and postsynaptic sites. The models presented here constitute appropriate examples of this transynaptic mode of steroid and, therefore, may offer a useful approach to investigate steroid hormone actions on the brain.

Partial characterization of a thyrotropin releasing hormone-sensitive glycosyl-phosphatidylinositol in pituitary lactotrophes.

Metabolic labelling experiments performed with cultured pituitary lactotrophes revealed the presence of a glycosyl-phosphatidylinositol (GPtdIns) structurally related to GPtdIns lipids isolated from other cell types as demonstrated by: (i) metabolic incorporation of [3H]galactose, [3H]glucosamine and [3H]inositol into the polar inositolphosphoglycan moiety (InsPG) and [3H]myristate and [3H]palmitate into the diacylglycerol (DAG) backbone of GPtdIns; (ii) sensitivity of the [3H]labelled GPtdIns to nitrous acid deamination and; (iii) sensitivity of GPtdIns to phosphatidylinositol (PtdIns)-specific phospholipase C (PLC) hydrolysis. In cultured pituitary cells labelled to isotopic steady state with 10 microCi/ml of [3H]glucosamine, treatment with hypothalamic TRH (10(-6) M) induced a rapid and transient hydrolysis (ca. 50%) of the labelled GPtdIns. Moreover, as demonstrated in [3H]inositol labelled cells, treatment with thyrotropin releasing hormone (TRH) elicited the cleavage of [3H]GPtdIns in a similar manner, and this effect was followed by the phosphoinositide (PtdIns, PtdInsP and PtdInsP2) hydrolysis 30 s later. These results suggest that the phosphodiesterase cleavage of GPtdIns could be an early event implicated in TRH action in pituitary lactotrophes.