Endothelin-1, endothelin converting enzyme-1 and endothelin receptors in the porcine corpus luteum.

Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2alpha (PGF-2alpha) (ie, luteolytic sensitivity [LS]) until about day 12-13 of the estrous cycle. Although little is known of the control of LS in any species, endothelin-1 (EDN1) is believed to play a role in LS control in ruminants. Therefore, we measured mRNA and protein expression and examined the cellular localization of EDN1 precursor (pre-pro EDN1, or ppEDN1), EDN-converting enzyme-1 (ECE1), and EDN receptors (A, EDNRA and B, EDNRB) in porcine CLs collected on days 4, 7, 10, 13, and 15 of the estrous cycle to look for differences between CLs displaying (days 13-15) versus those lacking (days 4-10) LS. Abundance of ppEDN1 mRNA was greatest (and significant vs all other days) on day 7 of the cycle, whereas EDN1 protein expression did not vary during the cycle and was localized exclusively to endothelial cells (EC). Abundance of ECE1 mRNA was also greatest on day 7 (vs all other days), but ECE1 protein was significantly elevated on day 10 (vs day 4) and was immunolocalized to ECs and large luteal cells (LLC). Abundance of EDNRA mRNA was also maximal on day 7 (vs all other days) of the cycle, whereas EDNRA protein expression was not significantly changed during the cycle and was observed in LLCs, ECs, and small luteal cells (SLC). On day 13, EDNRB mRNA was significantly decreased (versus day 7). Expression of EDNRB protein was decreased on day 10 (versus all other days), and on days 13-15 (vs day 4), and was primarily localized to ECs. In conclusion, the observed elevation in ECE1 protein concentrations on day 10 and the presence of EDNRA on LLC suggests a possible role for EDN1 (resulting from the actions of ECE1) acting via EDNRA in the control of LS in the pig.

The role of intra-luteal factors in the control of the porcine corpus luteum.

In this paper we review three intra-luteal factors and their roles in the corpus luteum (CL). Insulin-like growth factor (IGF)-I, together with its receptor and IGF-binding proteins (IGFBPs), represent an important control system in the CL. IGF-I is a product of small luteal cells and has steroidogenic (i.e. luteotrophic) actions on large luteal cells via the type I receptor, while IGFBPs (e.g. BP-2 and 3; small cells) generally inhibit IGF-Is actions. IGF-I is particularly important in early CL development (up to day 7 of the oestrous cycle) in the pig. Tumour necrosis factor (TNF)-alpha is a product of luteal macrophages that infiltrate CLs in increasing numbers as the cycle progresses. TNF-alpha has been shown to play an important role in luteolysis, but we hypothesise that in the pig, this factor plays an additional role during the mid-luteal phase (days 7-13) in promoting the acquisition of luteal sensitivity to the luteolytic actions of prostaglandin (PG)F2alpha (= luteolytic sensitivity; LS). Endothelin (ET)-1 is a product of (luteal) endothelial cells, and along with its receptors (ETA and ETB) and endothelin-converting enzyme (ECE)-1, represent an intra-luteal system that also plays a role in luteolysis, in association with PGF2alpha. Since TNF-alpha induces endothelial cells to secrete ET-1, we hypothesise that ET-1 mediates the sensitising effects of TNF-alpha on the porcine CL during the mid-luteal phase (days 7-13). Finally, we hypothesise that TNF-alpha and/or ET-1 act to up-regulate luteal protein kinase C (e.g. isoforms betaII and epsilon) activity and thereby sensitises luteal cells to PGF2alpha.