INTERFERENCE OF SEX-RELATED FACTORS IN THE RESPONSE OF LIVER CELLS TO EXPERIMENTAL MITOTIC STIMULI

Stimulation of liver cell multiplication was obtained under two different experimental conditions.

• 1 A single injection of casein solution resulted in (a) an identical synchronized mitotic wave response in 10-day old male and female rats and (b) a significantly lower response in adult male rats compared to females, a difference which was reduced by castration of males at birth but essentially maintained if animals were operated when 10 days old.
• 2 Partial hepatectomy shortly after puberty resulted in active hepatocyte multiplication occurring 3 hr earlier in females than in males. This difference was suppressed when females were ovariectomized at birth and significantly reduced when they were spayed at a later age. Hepatocytes of castrated females entered actively into S phase 2 hr later than the sham-operated controls. Unilateral ovariectomy on the other hand indicated that during compensatory and/or hyper-compensatory activity of the single ovary there was a maximum difference between the male and female rate of [³H]thymidine uptake in liver nuclei 20 hr after hepatectomy. A further kinetic study (t= 25, 30, 40, 65, 90 hr) indicated no significant sex-related difference in the number of S phases per 10,000 cells.

The DNA content of regenerating versus control livers was comparable in both sexes at t= 22 and 90 hr but higher in females at t= 40 and 65 hr. A possible early postnatal interference of certain hormonal mechanisms in the receptivity to mitotic stimuli is postulated and discussed.