Thoughts on Leigh's data re: endothelial steroidogenesis.

(1)
I would be surprised if endothelial cells could synthesize steroids de novo
since, to the best of my knowledge, they isn't the prerequisite uptake,
metabolism or synthesis of cholesterol in these cells. Can't recall any
reports of P450 cholesterol side-chain cleavage in these cells, and without
P450CSCC, they'd have to rely on steroid precursors (pregnenolone and
androstenedione for 3=DFHSD and P450-Aromatase respectively) from the
neighbouring theca. I would have thought (though with no firm basis) that
the contribution of endothelial enzymes (if any) to ovarian steroid output
would be negligible relative to granulosa and thecal cell 3=DFHSD and AROM.
Unless, of course, anyone knows otherwise?

(2)
Would have thought that this was an ideal opportunity to use molecular
techniques to help address a question (rather than just for the hell of
it!). By comparing ISH to IHC data, could establish the likelihood that the
3=DFHSD and AROM antisera are detecting real proteins. Rather suspect that=
the signals may be artefacts in the absence of complementary enzyme activity or
mRNA data.

(3)
Worth bearing in mind that Ed Milgrom has shown endothelial cells express LH
receptors implicated in the transcytosis of LH from the endothelial lumen to
the gonadal target cells. This raises two possibilities:
(a) That LH activates the cAMP system in endothelial cells to upregulate
expression of 3=DFHSD and P450 AROM almost coincidentally. However, would
expect upregulation of P450C17 (17a-hydroxylase) if this were true.
(b) LH is actually regulating a functional steroidogenic pathway in
endothelial cells!


Lots of thoughts but no data I'm afraid!!!

Tony Michael

Dr.Tony Michael
Lecturer in Biochemistry & Molecular Biology,
Dept.Biochemistry & Molecular Biology,                       Tel : 0171-794-0500 x.4999 (Office)
Royal Free Hospital School of Medicine,                      Tel: 0171-794-0500 x.4988 (Lab)
Rowland Hill Street,
Fax : 0171-794-9645
London NW3 2PF