It is with sadness for
a life cut short that we note the recent death of Dr Ziggy Krozowski, who made
ground-breaking contributions to steroid receptor biology in general, and to
aldosterone action in particular.
Ziggy grew
up in Perth, part of the post-war Polish diaspora, where he did his
undergraduate degree and Ph.D. His first post-doctoral position was with the
late Rob Sutherland at the Garvan Institute, working on oestrogen receptors in
breast cancer.
He then moved to the Medical Research Centre at Prince Henry's
Hospital in Melbourne, to work with John Funder on mineralocorticoid receptors
and aldosterone. In 1991 he published two papers in Endocrinology, on MR in
pituitary and lung, questioning their then undisputed uniquely epithelial
location; in 1982 a JCI paper distinguishing classical GR from the
"corticosterone-preferring receptors" in the pituitary; and in 1983 a
seminal PNAS paper showing the identity of hippocampal "corticosterone-preferring"
receptors and renal MR.
Given the known equivalent affinity for the
physiological glucocorticoids and aldosterone for MR, this posed the question -
fair and square - of how aldosterone could selectively activate renal MR, in
the face of ~1000-fold higher circulating glucocorticoid levels.
Ziggy put the question on hold, and went off on a CJ Martin
Fellowship to Pierre Chambon's laboratory in Strasbourg, one of the epicentres
of receptor molecular biology. Here he learned high-end molecular techniques,
and wrestled with the French language and the eventful cloning of the
progesterone receptor.
Back home at Prince Henry's he returned to the enigma of
the epithelial selectivity of the MR for aldosterone. This had become clearer
despite his absence by the identification of the crucial role of the enzyme
11-beta hydroxysteroid dehydrogenase (11BHSD) in the kidney tubule, converting
cortisol but not aldosterone to receptor-inactive metabolites.
Ziggy set to, to
isolate and then clone 11BHSD, at Prince Henry's and subsequently at the Baker
Institute. The way was not easy. What was initially considered a single enzyme
was in fact two - the 'liver' enzyme 11BHSD1, and the 'renal' enzyme 11BHSD2,
with very different activities. Ultimately he succeeded, publishing the human
gene sequence of 11BHSD2 before a group in Texas published that in the sheep, a
nice inversion of national stereotypes.
Ziggy was quiet, undemonstrative and generous to a fault. He
collaborated freely and widely - while at Prince Henry's with the inhibin
group; from the Baker providing reagents for the MR/HSD2 community world-wide;
in studies with Maria New in New York on HSD2 mutations, leading to Apparent
Mineralocorticoid Excess; on studies during brief sabbaticals with Paul Stewart
in Birmingham, and with Elise and Celso Gomez Sanchez in the USA.
He brought
molecular biology to the Baker, mentored a group of very successful (and on
occasion difficult) post-docs and devoted research assistants, and published a
total of 140 papers - 80 of which are on 11BHSD2.
He retired early, not long after the untimely death of his
first wife Sabina. Ziggy loved fishing, and had divided football allegiances -
to soccer, in the broad, and the AFL (Eagles, of course).
Like many quiet
achievers he was much better recognized internationally than in Australia. He
will live on, in the memory of Barbara, his wife of the precious few last
years; in the many memories of his family, colleagues and friends; and in his
monumental contribution to one of the
key questions in cardiovascular endocrinology.
Tim Cole/ Peter Fuller/ John Funder.
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