Ity of Nursing and Health Sciences, Taipei City 112, Taiwan Institute of Sports Sciences, TRPV Agonist Purity & Documentation University of Taipei, Taipei City 112, Taiwan Correspondence: [email protected] (Y.-H.L.); [email protected] (S.-C.T.) Equally contributed to this perform.Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Abstract: The objective of this study would be to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells as well as the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells have been cultured with different test drugs within the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level have been measured. On top of that, the cytosolic-free Ca2+ concentrations ([Ca2+ ]i) were measured to examine the function of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited each basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 substantially decreased progesterone and estradiol basal release but failed to improve a further amphetamine inhibitory effect. Amphetamine was capable of additional suppressing the release of estradiol release below the presence of nifedipine. Pretreatment together with the amphetamine for two h decreased the basal [Ca2+ ]i and prostaglandin F2-stimulated raise of [Ca2+ ]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells by way of a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our existing findings show that it is necessary to study the PDE2 Inhibitor supplier possibility of amphetamine perturbing reproduction in females. Keywords and phrases: reproductive hormones; follicle-stimulating hormone (FSH) administration; steroidogenic enzymes; protein kinase A (PKA); L-type calcium channelCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short article is definitely an open access article distributed below the terms and conditions with the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).1. Introduction Amphetamine, an indirect dopamine agonist, was initially discovered 100 years ago. Since then, a lot of research have confirmed that amphetamine influences the central and peripheral nervous program by acting around the activities of monoamine reuptake transporters.Biomedicines 2021, 9, 493. https://doi.org/10.3390/biomedicineshttps://www.mdpi.com/journal/biomedicinesBiomedicines 2021, 9,two ofThe functional responses altered by amphetamine contain reduced reaction time [1], antifatigue [2] and impaired cognition [3]. An acute overdose of amphetamine causes impairment of executive brain function and leads to severe drug addiction [4], and chronic intake of amphetamine might be related with grave and also fatal side-effects [5]. In addition, Huybrechts et al., reported that amphetamine exposure in pregnancy will enhance the danger of congenital malformations compared with no exposure to stimulants [6]. There is poor obstetric history in females addicted to amphetamine including a higher incidence of preceding abortion, preeclampsia, infection and antepartum hemorrhage [7]. In endometrial tissue, progesterone levels are 200 occasions larger in fertile girls than in these with habitual.