Adenosine triphosphate inhibits LH stimulated testosterone accumulation by isolated rabbit ovarian follicles

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Testosterone is a major secretory product of the rabbit follicle. Work from our laboratory also suggests that the steroidogenic responses of the follicles to LH and cAMP are different in that the LH effects were more long lasting whereas the response to cAMP could be evoked at will. Cyclic AMP is accepted as the second messenger which mediates the steroidogenic response to LH. It was therefore of interest to determine whether different responses could be elicited when LH and nucleotides were added together to isolated rabbit follicles. Unless otherwise stated procedures used were similar to those previously described. It was not determined whether ATP inhibited the binding of LH to the follicular cells. This possibility must be considered since the binding of HCG to bovine corpora lutea membranes can be inhibited by nucleotides. Although ATP could have inhibited LH binding it is apparent that this inhibition is not complete since testosterone production could be observed after the ATP was removed (panel e, final 2 h of incubation). The resumption of steroidogenesis after the removal of ATP is similar to data obtained with inhibitors of protein synthesis and lends further support to our contention that LH binding to follicular cells initiates an irreversible series of events which can be delayed at sites beyond gonadotropin binding, by various inhibitors.

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... Oocyte maturation in the mouse is stimulated by a surge of LH 12 hours prior to ovulation. ATP was shown to inhibit LHstimulated testosterone accumulation by isolated ovarian follicles from rabbits [325]. Adenosine produced a seven-fold amplification of LH-stimulated cAMP accumulation and progesterone secretion in rat luteal cells, but did not show a similar effect on LH-stimulated cAMP accumulation and androgen secretion in luteal cells [208]. ...
There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5'-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.
Purinergic effects in vivo are local, specific, transient, and affect target cells in a paracrine or autocrine manner. Purinergic signalling is involved in the regulation of numerous functions in the male and female reproductive tract organs. Analysis of functional expression of purinoceptors suggests that P2Y2 receptors are involved in the regulation of luminal fluid secretion in vivo; P2X1 and P2X2 in the regulation of smooth muscle cell contraction of blood vessels and tubular organs; P2X2 in the regulation of sperm cell maturation; P2X3 in activation of sensory nerve fibers involved in reflex activities and pain; P2X4 in the regulation of tight junctional resistance and epithelial transport in female reproductive tract epithelia, and in the regulation of luminal acidification in the epididymis, vas deferens and probably the vagina and ectocervix; P2Y1 and P2Y2 in the regulation of cell proliferation; P2X5 and P2X7A in the regulation of epithelial cell terminal differentiation and apoptosis; and A1 receptors in the regulation of sperm cell capacitation. Translational studies suggested that cellular levels of the P2X7A receptor could be used as a biomarker for the early detection of breast, ectocervix, endocervix, endometrial and bladder cancers. Data also suggested that the P2X7A mechanism could be used as a pharmaceutical target for the prevention and treatment of epithelial neoplasia through the induction of apoptosis. Copyright © 2015 Elsevier B.V. All rights reserved.
There are multiple roles for purinergic signalling in both male and female reproductive organs. ATP, released as a cotransmitter with noradrenaline from sympathetic nerves, contracts smooth muscle via P2X1 receptors in vas deferens, seminal vesicles, prostate and uterus, as well as in blood vessels. Male infertility occurs in P2X1 receptor knockout mice. Both short- and long-term trophic purinergic signalling occurs in reproductive organs. Purinergic signalling is involved in hormone secretion, penile erection, sperm motility and capacitation, and mucous production. Changes in purinoceptor expression occur in pathophysiological conditions, including pre-eclampsia, cancer and pain.
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