Neurotransmitter-controlled steroid hormone receptors in the central nervous system

Results are discussed indicating that neurotransmitters affect steroid hormone activity not only by controlling via neuroendocrine events the hypophysial-gonadal and hypophysial-adrenal axes, but also by modulating cell responsiveness to steroids in target cells. Hyper- or hypoactivity of pineal nerves result in enhancement or impairment of estradiol and testosterone effects on pineal metabolism in vivo and in vitro. Pineal cytoplasmic and nuclear estrogen and androgen receptors are modulated by norepinephrine released from nerve endings at the pinealocyte level. Neural activity affects the cycle of depletion-replenishment of pineal estrogen receptors following estradiol administration. Another site of modulation of steroid effects on the pinealocytes is the intracellular metabolism of testosterone and progesterone; nerve activity has a positive effect on testosterone aromatization and a negative effect on testosterone and progesterone 5α-reduction. NE activity on the pineal cells is mediated via β-adrenoceptors and cAMP. In the central nervous system information on the neurotransmitter modulation of steroid hormone action includes the following observations: (a) hypothalamic deafferentation depresses estrogen receptor levels in rat medial basal hypothalamus; (b) changes in noradrenergic transmission affect, via α-adrenoceptors, the estradiol-induced increase of cytosol progestin receptor concentration in guinea pig hypothalamus; (c) cAMP increases testosterone aromatization in cultured neurons from turtle brain; (d) electrical stimulation of dorsal hippocampus augments, and reserpine or 6-hydroxydopamine treatment decrease, corticoid binding in cat hypothalamus. In the adenohypophysis changes in dopaminergic input after median eminence lesions or bromocriptine treatment of rats result in opposite modifications of pituitary estrogen receptor levels. Therefore all these observations support the view that neurotransmitters can modulate the attachment of steroid hormones to their receptors in target cells.     

Release and specific binding of prostaglandins in bovine pineal gland

Incubated bovine pineal glands released prostaglandin E- and prostaglandin F-like material (304 ± 20 and 582 ± 56 pg/mg dry tissue wt/h, respectively) and the release was increased 2.2 2.9-fold by adding 10⁻⁴–10⁻⁶M of norepinephrine to the medium. Binding assays revealed the existence of high affinity binding of ³H-prostaglandin E₂ (³H-PGE₂) and ³H-prostaglandin F_2α (³H-PGF_2α) in low speed supernatants of pineal homogenates. Binding was increased by increasing Ca⁺⁺ concentration in medium up to 2 mM, was heat-labile and was depressed following incubation with trypsin. In subcellular fractionation studies maximal ³H-PG binding was found in the 27000 × g pellet. Scatchard analysis of ³H-PGE₂ binding revealed the presence of a single population of binding sites with a K_d= 1.2 nM and a binding site concentration of 1–2 pmoles/g protein. A single population of binding sites for ³H-PGF_2α was also detected with a K_d= 1.7 nM and a similar binding site concentration. Non-radioactive PGE₁ and PGE₂ were almost equally effective to compete for ³H-PGE₂ binding sites (ED₅₀= 5 and 2 nM, respectively). Unlabeled PGF₂ was relatively ineffective to compete for ³H-PGE₂ binding (ED₅₀>1000 nM) but displaced effectively ³H-PGF_2α binding (ED₅₀= 1.2 nM).