PMID- 35109967 OWN - NLM STAT- MEDLINE DCOM- 20220316 LR - 20220531 IS - 1448-5990 (Electronic) IS - 1031-3613 (Linking) VI - 34 IP - 3 DP - 2022 Feb TI - Interrelationships between amphiregulin, kisspeptin, FSH and FSH receptor in promotion of human ovarian cell functions. PG - 362-377 LID - 10.1071/RD21230 [doi] AB - The aim of this study was to investigate: (1) the ability of granulosa cells to produce amphiregulin (AREG), kisspeptin (KISS) and FSH receptor (FSHR); (2) the role of AREG and KISS in the control of ovarian functions; (3) the effect of FSH and KISS on AREG; and (4) the ability of KISS to affect FSHR and to modify FSH action on AREG output by human ovarian granulosa cells. We examined: (1) time-dependent accumulation of AREG; (2) effects of AREG (0, 1, 10, 100ng/mL) and KISS (0, 1, 10, 100ng/mL) on granulosa cell functions; and (3) the effects of KISS (0, 1, 10, 100ng/mL), FSH (0, 1, 10, 100ng/mL), and their combinations on AREG release. Viability, markers of proliferation [accumulation ofproliferating cell nuclear antigen (PCNA) cyclin B1 and sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy6-nitro)benzene sulfonic acid hydrate (XTT formazan)] and apoptosis (accumulation of bax, caspase 3 and terminal deoxynucleotidyl transferase dUTP nick-end labelling), accumulation of KISS, FSHR and steroid hormones, and AREG release were analysed by Trypan blue exclusion test, quantitative immunocytochemistry, XTT, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays and enzyme-linked immunosorbent assay. AREG promoted cell viability, proliferation and steroid hormone output, and inhibited apoptosis. KISS (1 and 10ng/mL) stimulated viability, proliferation, steroid hormone release and occurrence of FSHR and suppressed apoptosis and AREG output; KISS (100ng/mL) had the opposite effect. FSH stimulated AREG release, whilst addition of KISS reversed this FSH effect. FSH mimicked and promoted the inhibitory effect of KISS on AREG release. These results suggest an intra-ovarian production and a functional interrelationship between AREG, KISS, FSH and FSHR in direct regulation of basic ovarian cell functions. FAU - Fabova, Zuzana AU - Fabova Z AD - Department of Zoology and Anthropology, Constantine the Philosopher University, Tr. A. Hlinku 1, 94974 Nitra, Slovakia. FAU - Loncova, Barbora AU - Loncova B AD - Department of Zoology and Anthropology, Constantine the Philosopher University, Tr. A. Hlinku 1, 94974 Nitra, Slovakia. FAU - Mlyn Ek, Milos AU - Mlyn Ek M AD - Department of Zoology and Anthropology, Constantine the Philosopher University, Tr. A. Hlinku 1, 94974 Nitra, Slovakia. FAU - Sirotkin, Alexander V AU - Sirotkin AV AD - Department of Zoology and Anthropology, Constantine the Philosopher University, Tr. A. Hlinku 1, 94974 Nitra, Slovakia. LA - eng PT - Journal Article PL - Australia TA - Reprod Fertil Dev JT - Reproduction, fertility, and development JID - 8907465 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (FSHR protein, human) RN - 0 (Follicle Stimulating Hormone, Human) RN - 0 (KISS1 protein, human) RN - 0 (Kisspeptins) RN - 0 (Receptors, FSH) RN - 9002-68-0 (Follicle Stimulating Hormone) SB - IM MH - Amphiregulin/*metabolism/pharmacology MH - Apoptosis MH - Cell Proliferation MH - Cells, Cultured MH - Female MH - Follicle Stimulating Hormone/pharmacology MH - Follicle Stimulating Hormone, Human/*metabolism MH - Granulosa Cells MH - Humans MH - Kisspeptins/*metabolism/pharmacology MH - Ovary/*cytology/*physiology MH - Receptors, FSH/*metabolism EDAT- 2022/02/04 06:00 MHDA- 2022/03/17 06:00 CRDT- 2022/02/03 05:28 PHST- 2021/08/17 00:00 [received] PHST- 2021/11/16 00:00 [accepted] PHST- 2022/02/04 06:00 [pubmed] PHST- 2022/03/17 06:00 [medline] PHST- 2022/02/03 05:28 [entrez] AID - RD21230 [pii] AID - 10.1071/RD21230 [doi] PST - ppublish SO - Reprod Fertil Dev. 2022 Feb;34(3):362-377. doi: 10.1071/RD21230.