The Nobel Prize
in Chemistry 1939
The following account of Butenandt's work has been made.
As recently as twelve years ago, very little was known about
the nature of the sex hormones. As regards the oestrogenic, or follicle, hormone
it was established that extracts from certain organs, e.g. the ovaries and placenta,
bring about the characteristic
oestrus phenomena in castrated female rats. Only
a few observations were available concerning the stability and solubility of
their active principles. Further development in the chemistry of the oestrogenic
hormones could not take place until the purely biological discoveries by Allen
and Doisy in 1923 and by Aschheim and Zondek in 1927 had been made.
Butenandt made the first big step forward in clarifying the chemistry of the
follicle hormone in 1929 in Göttingen, simultaneously with Doisy in the
United States. Both workers succeeded in isolating from the urine of pregnant
women a substance in crystalline form having oestrogenic effects. Butenandt
named this substance folliculine, a designation which was later changed to oestrone.
He established that its empirical formula was C18H22O2,
and that it was an oxyketone.
Shortly after the discovery of oestrone, Marrian in London (1930) isolated from
the urine of pregnant women a new hormone which he called oestriol. Butenandt
confirmed Marrian's discovery and explained the relationship between the new
substance and oestrone. The relation between sterols and oestrogenic substances
which had been assumed on crystallographical grounds became probable from the
chemical point of view only after Butenandt and Marrian had shown, independently
of one another, that only three benzoide double bonds enter into the ring system
of these substances.
In 1932, Butenandt was able, from observations made in spectral analysis, and
especially on the basis of the then established correct formula of cholesterol
to draw up the formulae of the chemical structure of oestrone and oestriol.
But there remained the important task of proving the chemical structure of the
ring system as assumed by Butenandt. By breaking down the oestriol molecule
stage by stage Butenandt proved that both œstrogenic hormones contained
a phenanthrene core. At the same time he was able to obtain the same dimethyl
phenanthrene from etiobilianic acid, a transformation product of cholic acid.
He had thus confirmed the close relationship existing between the follicle hormones
on the one hand and the bile acids and
sterols on the other.
The second important ovarian hormone, the corpus luteum hormone, was by various
workers obtained in crystalline form from corpus luteum in 1931 and 1932. In
1934, Butenandt and Westphal succeeded in producing this hormone, which was
given the name progesterone, in a chemically pure form. They also demonstrated
its close relationship with sites in Nobel Prize beast Chemistry male pregnanediol, Nobel Chemistry in freek panty Prize a Chemistry Prize Nobel in rape mudshark stories physiologically Chemistry rough Prize in stories Nobel sex inactive dihydric
alcohol which in male beast Prize Chemistry sites Nobel Butenandt and Marrian had found independently of one another in
the urine of pregnant women. In the autumn of 1934, Butenandt succeeded in converting
pregnanediol into progresterone. The synthesis of this important pregnancy hormone
from cholesterol was carried out by Butenandt in a simple way in 1939.
The merit of the chemical exploration of the testicular, or androgenic, hormones
falls to Butenandt and Ruzicka in common. Butenandt was the first to tackle
this problem, and it was only possible to work on it after biological research
had found a quantitative test for the determination of these substances - the
so-called capon comb test.
Butenandt started with male urine, or
alternatively its chloroform extract -
approximately 0.8 per thousand dissolved in chloroform. In the process of purification
it proved that the male hormone behaved in many respects like oestrone; when
he realized this, it made Butenandt's work considerably easier.
When the purification had been successfully accomplished, there presented for
the first time a crystalline substance with the physiological properties of
a male sex hormone.
Butenandt gave this substance the name androsterone and defined its composition
as C19H30O2. It differs from oestrone only
in the additional content of 1 methyl group and 5 hydrogen atoms. Butenandt
drew up the full constitutional formula in
1934 on the basis of the formula
of cholesterol.
Androsterone had been synthesized from epi-cholestanol by Ruzicka, but it soon
proved to be not identical with the genuine male hormone from the testicles.
For this reason it made a great stir when in 1935 Laqueur and his collaborators
isolated from testicular extract a highly active hormonetestosterone.
The close relationship of testosterone to androsterone made it comparatively
easy to clarify its chemical composition, and still in the same year 1935 Ruzicka
and Butenandt were able, in the same way but
independently of each other, to
obtain testosterone from trans-dehydro-androsterone.
Butenandt, Ruzicka and others then produced from sterols various new substances
which, when tested as male sex hormones, were found to be active in varying
degrees.*
* Professor Adolf Butenandt was awarded half of the Nobel
Prize in Chemistry for 1939, for his work on sex hormones. Owing to political
conditions at the time, Professor Butenandt was prevented from accepting the
prize. In 1949 he received the gold medal and the diploma.