Follicle-stimulating hormone and luteinizing hormone increase Ca2+ in the granulosa cells of mouse ovarian follicles†

Abstract

In mammalian ovarian follicles, follicle stimulating hormone (FSH) and luteinizing hormone (LH) signal primarily through the G-protein Gs to elevate cAMP, but both of these hormones can also elevate Ca2+ under some conditions. Here, we investigate FSH- and LH-induced Ca2+ signaling in intact follicles of mice expressing genetically encoded Ca2+ sensors, Twitch-2B and GCaMP6s. At a physiological concentration (1 nM), FSH elevates Ca2+ within the granulosa cells of preantral and antral follicles. The Ca2+ rise begins several minutes after FSH application, peaks at ∼10 min, remains above baseline for another ∼10 min, and depends on extracellular Ca2+. However, suppression of the FSH-induced Ca2+ increase by reducing extracellular Ca2+ does not inhibit FSH-induced phosphorylation of MAP kinase, estradiol production, or the acquisition of LH responsiveness. Like FSH, LH also increases Ca2+, when applied to preovulatory follicles. At a physiological concentration (10 nM), LH elicits Ca2+ oscillations in a subset of cells in the outer mural granulosa layer. These oscillations continue for at least 6 h and depend on the activity of Gq family G-proteins. Suppression of the oscillations by Gq inhibition does not inhibit meiotic resumption, but does delay the time to 50% ovulation by about 3 h. In summary, both FSH and LH increase Ca2+ in the granulosa cells of intact follicles, but the functions of these Ca2+ rises are only starting to be identified.

Document Details

Document Type
Pub Defense Publication
Publication Date
May 14, 2019
Source ID
10.1093/biolre/ioz085

Entities

People

  • Alexei V Evsikov
  • Andreas S Tolias
  • C. M. Owen
  • Jacob Reimer
  • Jeremy R Egbert
  • Laurinda A Jaffe
  • Oliver Griesbeck
  • Paul G Fahey
  • Russell S Ray
  • Viacheslav O Nikolaev

Organizations

  • Baylor College of Medicine
  • Intelligence Advanced Research Projects Activity
  • National Institutes of Health
  • University Medical Center Hamburg-Eppendorf
  • University of Connecticut

Tags

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Mathematics or Statistics
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology