Interrelationships between amphiregulin, kisspeptin, FSH and FSH receptor in promotion of human ovarian cell functions.
Fabová. Zuzana Z; Loncová. Barbora B; Mlyn Ek. Miloš M; Sirotkin. Alexander V AV
Key Findings
- Low‑dose kisspeptin (1‑10 ng/mL) improves granulosa cell viability, proliferation, and steroid hormone output.
- High‑dose kisspeptin (100 ng/mL) reduces these beneficial effects and increases apoptosis.
- Kisspeptin can suppress FSH‑induced amphiregulin (AREG) release, indicating a dose‑dependent regulatory role.
Practical Outcomes
- For women interested in supporting ovarian health, low‑dose kisspeptin might be beneficial, but higher doses could be harmful. Any self‑experiment should start with very low concentrations and monitor hormone levels and ovarian markers. Clinical relevance is still uncertain, so proceed with caution and consider medical guidance.
Summary
The study shows that kisspeptin-10 can boost ovarian cell health at low concentrations (1‑10 ng/mL) by increasing cell survival, growth, and hormone production, while a high dose (100 ng/mL) does the opposite. It also reveals that kisspeptin can block the hormone‑driven release of another growth factor (AREG) that FSH normally stimulates.
Abstract
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.
Study Information
pubmed
2022
10.1071/rd21230