Relaxin triggers calcium transients in human granulosa-lutein cells

Abstract

Although the peptide hormone relaxin is synthesized by the human corpus luteum in vivo, its potential to serve as a local factor in the regulation of luteal function is not clear. Using an enzyme-linked immunosorbent assay for human relaxin, we detected relaxin in the culture medium of human granulosa-lutein cells as early as after 6 days in culture. Moreover, 1 x 10(5) IU/l human chorionic gonadotropin stimulated relaxin release about fourfold during a 48-h incubation on culture days 6-8 (and 7-9), but not earlier (on days 1, 3 and 4). The stimulatory action of human chorionic gonadotropin on progesterone release was not influenced by relaxin, and relaxin alone was without stimulatory effect. However, human recombinant relaxin (between 0.1 and 12.5 micrograms/l) increased intracellular free Ca2+ basal levels to maximal peak levels exceeding 1000 nmol/l in about 64% of all tested cells (N = 168) with no obvious dependency on the culture day. The relaxin-induced Ca2+ signal was not affected by removal of extracellular Ca2+. As depletion of intracellular Ca2+ stores by ionomycin rendered the cells unresponsive to relaxin or diminished their ability to respond, these results point to an intracellular source of the Ca2+ signal. In summary, our data indicate the presence of a functional relaxin receptor on human granulosa-lutein cells, which is linked to Ca2+ release from intracellular stores.

Comparison of relaxin receptors in rat isolated atria and uterus by use of synthetic and native relaxin analogues

“…In an in vivo study in rat, relaxin induced only small increases in myometrial cyclic AMP in comparison to salbutamol, a β 2 ‐adrenoceptor agonist (Downing et al , 1992). In human granulosa‐lutein cells, relaxin released Ca 2+ from intracellular stores possibly via activation of IP 3 ‐PKC (Mayerhofer et al , 1995). These observations indicate that both IP 3 and cyclic AMP may be utilized in signal transduction.…”

Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin

“…There has been much debate on the signalling mechanism utilized by relaxin. Earlier studies suggested that cyclic AMP (cAMP) (Han et al ., 1994), inositol trisphosphate (Mayerhofer et al ., 1995) or ATP‐sensitive K + channels (Noack et al ., 1992) were involved. Relaxin, like isoprenaline, produces powerful inotropic and chronotropic effects in rat atria (Kakouris et al ., 1992).…”

Identification of Voltage‐Activated Na+ and K+ Channels in Human Steroid‐Secreting Ovarian Cells

“…Like their counterparts in the corpus luteum, these cells produce progesterone, which is crucial for maintaining pregnancy. As shown previously, these cells possess receptors for various hormones and neurotransmitters (e.g., oxytocin, relaxin, catecholamines, acetylcholine 4–7), and activation of these receptors is linked to increased Ca 2+ , which is mainly, though not exclusively derived from intracellular stores. In an attempt to further characterize the signal transduction machinery of these cells, we have now started to examine their as yet unknown electrophysiological properties.…”