FSH induces Ca2+ uptake upon partial degradation

What is it about?

We have previously reported that synthetic peptide amides corresponding to regions of the β-subunit of human FSH [hFSH-β-(l-15) and hFSH-β-(51-65)J have the ability to bind calcium and to facilitate its entry into liposomes. In the present study, we have examined the ability of synthetic peptides corresponding to the entire primary structure of hFSH-d-subunit, to induce calcium influx in cultured rat Sertoli cells. Calcium (as45Ca2+) uptake in response to 50 hFSH-β-(l-15), hFSH-β-(21-35), or hFSH-β-(51-65) peptide amides was 2.5-, 2.4-, and 2.0-fold higher, respectively, than basal uptake. Pretreatment of Sertoli cells for 5 min with phenylarsine oxide (PAO, 80 fiM), an inhibitor of receptor-mediated endocytosis, significantly (P < 0.05) reduced45Ca2+influx in response to hFSH-d-(l-15), hFSH-β-(21-35), and hFSH-fl-(51-65). A delay of 20 min was required, however, before the inhibitory effect of PAO on45Ca2+ uptake was observed. Specific binding of [125I] hFSH to receptor at 4 C was unaffected by PAO. After 2 h at 37 C, however, approximately 1.6-fold more [125I]hFSH specifically bound at 4 C could be dissociated from the cell surfaces of PAO-pretreated Sertoli cell monolayers, compared to untreated monolayers. This result is consistent with an inhibitory effect of PAO on FSH receptor internalization. Chloroquine (at 100 fiM), a lysosomotropic agent known to block FSH degradation, also significantly (P < 0.05) inhibited FSH-induced45Ca2+uptake. Extending our earlier studies, these results suggest that the sustained (>20 min) phase of FSH-induced calcium uptake, also seen in response to synthetic hFSH- β -(l-1.5), hFSH- β -(21-35), and hFSH- β -(51-65) peptide amides, may occur as a consequence of FSH-receptor complex internalization and FSH degradation. Vesicular uptake of extracellular calcium, which accompanies internalization of FSH-receptor complexes, and release of channel-forming peptides by lysosomal hydrolysis of FSH suggests a novel mechanism whereby FSH increases intracellular calcium levels in Sertoli cells. © 1992 by The Endocrine Society.

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Why is it important?

It is interesting that fragments from FSH are able to permeabilize the endocytic membrane, as the results suggest, allowing Ca2+ transport.

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