HUMAN GRANULOSA-LUTEAL CELLS SECRETE PARATHYROID HORMONE-RELATED PROTEIN INVIVO AND INVITRO

The presence of mRNA transcripts and/or immunoreactivity for PTH-relat ed protein (PTHrP) in several normal mammalian tissues suggests a poss ible paracrine or autocrine role for this hormone. Since immunohistoch emical studies of human ovary demonstrate the presence PTHrP immunorea ctivity in this tissue, we wondered if ovarian follicular fluid (OVFF) might contain PTHrP. We retrospectively analyzed 28 OVFF samples obta ined at ova harvest in 21 women undergoing in vitro fertilization. Fou rteen samples contained significant adenylate cyclase-stimulating acti vity in a PTHrP-sensitive bioassay. In a subsequent prospective analys is, 41 of 45 freshly obtained OVFF samples demonstrated significant ac tivity. This bioactivity was completely neutralized by antisera to PTH rP, but was unaffected by antisera to PTH. Fifteen OVFF samples were a lso analyzed in a sensitive 2-site immunoradiometric assay for PTHrP, and all 15 demonstrated significant levels of the hormone. The PTHrP l evels did not correlate with the presence of an ovum in the follicle o r with follicular fluid calcium. Short term (24- to 48-h) cultures of granulosa-luteal cells established from 5 OVFF samples demonstrated co nstitutive secretion of PTHrP using the immunoradiometric assay. Neith er progesterone nor estrogen affected basal secretion. RNase protectio n analysis of cellular RNA prepared from cultured granulosa-luteal cel ls demonstrated the presence of mRNA for PTHrP in these cells. We conc lude that 1) human OVFF obtained after stimulation with FSH and LH con tain high concentrations of PTHrP; and 2) the granulosa-luteal cell is capable of secreting PTHrP both in vivo and in vitro.