Sources and function of neuronal signalling molecules in the gonads

While the hypothalamic-pituitary-gonadal axis is crucial for the function of the gonads, non-endocrine regulatory influences are exerted by other factors within the gonads. Among these factors are neurotransmitters, such as catecholamines. Several types of receptors for catecholamines exist in the gonads on vascular or endocrine cells. Their activation can alter blood flow, steroidogenesis and gene expression, depending on the target cells. Recently a neuronal-like cell type expressing catecholamine-biosynthetic enzymes and neuronal proteins was identified in testis and ovary of human and non-human primates. Together with the well-known sympathetic innervation, this gonadal nervous system may serve as a source of catecholamines. Dopamine is present in the follicular fluid. Oocytes, while not able to perform de novo synthesis of catecholamines, were shown to utilize dopamine to produce norepinephrine. This catecholamine then acts on beta-adrenoreceptors of follicular cells to increase cAMP. Oocytes may thus indirectly via dopamine and cAMP be able to control their own meiotic arrest. In addition, neurotransmitters may also be synthesized in other, non-neuronal ovarian cells. Thus, cultured human granulosa-luteal cells possess the acetylcholine synthesizing enzyme and the acetylcholine-specific vesicular transporter protein. These cells also express muscarinic-receptors (M1), which are linked to the mobilization of intracellular calcium and cell proliferation. This suggests involvement of the acetylcholine system in follicular growth and in the periovulatory events. In neurons, neurotransmitters alter the properties of the neuronal cell membrane. If this is the case in endocrine cells of the gonads is not yet clear, but the recent identification of voltage-activated potassium and sodium channels in human luteinized granulosa-luteal cells raises this question and opens a door to a new area of investigation.