16.
A C T I O N S O F H O R M O N E S
627
All 11 oestrogens including oestrone, diethylstilboestrol, equilin and
3,17j8 oestradiol, induced the formation of a squamous keratinizing
epithelium which displaced the original superficial mucified cells, but
there was a marked gradation of changes in different explants in each
group and a variation along the length of the explant. Dose-response
curves showed that the median effective dose was between 3-9 X 10~
6
/xg and 7-8 x I O
- 6 u.g, which is one-tenth of the median effective dose
required to produce comparable changes in the animal by intravaginal
application.
(b) Effects on alkaline phosphatase activity. In many tissues, positive
alkaline phosphatase activity is associated with active cell growth.
Koziorowska and Dux (1959) have shown that in rat and mouse vagina
grown in vitro this activity depends on the presence of sex hormones in
the medium. In fragments of rat and mouse vagina kept in medium
without hormones tests for alkaline phosphatase activity were usually
negative, but addition of either oestrone, oestradiol or stilboestrol
provoked a positive reaction, while a combination of oestradiol with
testosterone or progestrone produced a similar but weaker response. In
cultures of mouse vagina kept in defined medium, oestrone was one
hundred times less effective in eliciting a positive reaction than oestradiol, but in biological medium much smaller concentrations of
oestrone were sufficient for the same effect (Koziorowska, 1961). This
was probably due to the presence of oestrogenic hormones in the
biological medium which supplement and increase the activity of
oestrone.
(c) Effects on uterus and germinal epithelium. Oestrogens also affect other
female target tissues in vitro. Verne (1935) reported increased proliferation of rat uterine epithelium grown in plasma from rats previously
injected with oestrogen. Gaillard and de Jongh (1938) found a differential response of muscle, endometrium and epithelium of explants of
mouse uterus which depended on the concentration of the hormones
in the medium. After a dose of oestrone of 1/5000 i.u. the muscle layer
thickened appreciably and the epithelium, which in untreated cultures
became necrotic, was preserved. After 1 i.u. the muscle layers diminished in size but epithelium and endometrial connective tissue became
hypertrophic.
(d) Effects on male accessory sex organs. Price and Pannabecker (1956)
found that oestradiol stimulates the growth of the seminal vesicle of the
rat during embryonic development. Gaillard and de Jongh (1939)
obtained a similar stimulating effect of oestrone on the seminal vesicle
of young mice. The optimum growth-promoting concentration
differed for the various components of the gland; a dose of 1/50 i.u.
caused a maximal thickening of the smooth-muscle layer to three to
A C T I O N S O F H O R M O N E S
627
All 11 oestrogens including oestrone, diethylstilboestrol, equilin and
3,17j8 oestradiol, induced the formation of a squamous keratinizing
epithelium which displaced the original superficial mucified cells, but
there was a marked gradation of changes in different explants in each
group and a variation along the length of the explant. Dose-response
curves showed that the median effective dose was between 3-9 X 10~
6
/xg and 7-8 x I O
- 6 u.g, which is one-tenth of the median effective dose
required to produce comparable changes in the animal by intravaginal
application.
(b) Effects on alkaline phosphatase activity. In many tissues, positive
alkaline phosphatase activity is associated with active cell growth.
Koziorowska and Dux (1959) have shown that in rat and mouse vagina
grown in vitro this activity depends on the presence of sex hormones in
the medium. In fragments of rat and mouse vagina kept in medium
without hormones tests for alkaline phosphatase activity were usually
negative, but addition of either oestrone, oestradiol or stilboestrol
provoked a positive reaction, while a combination of oestradiol with
testosterone or progestrone produced a similar but weaker response. In
cultures of mouse vagina kept in defined medium, oestrone was one
hundred times less effective in eliciting a positive reaction than oestradiol, but in biological medium much smaller concentrations of
oestrone were sufficient for the same effect (Koziorowska, 1961). This
was probably due to the presence of oestrogenic hormones in the
biological medium which supplement and increase the activity of
oestrone.
(c) Effects on uterus and germinal epithelium. Oestrogens also affect other
female target tissues in vitro. Verne (1935) reported increased proliferation of rat uterine epithelium grown in plasma from rats previously
injected with oestrogen. Gaillard and de Jongh (1938) found a differential response of muscle, endometrium and epithelium of explants of
mouse uterus which depended on the concentration of the hormones
in the medium. After a dose of oestrone of 1/5000 i.u. the muscle layer
thickened appreciably and the epithelium, which in untreated cultures
became necrotic, was preserved. After 1 i.u. the muscle layers diminished in size but epithelium and endometrial connective tissue became
hypertrophic.
(d) Effects on male accessory sex organs. Price and Pannabecker (1956)
found that oestradiol stimulates the growth of the seminal vesicle of the
rat during embryonic development. Gaillard and de Jongh (1939)
obtained a similar stimulating effect of oestrone on the seminal vesicle
of young mice. The optimum growth-promoting concentration
differed for the various components of the gland; a dose of 1/50 i.u.
caused a maximal thickening of the smooth-muscle layer to three to