Rats were ovariectomized 2–4 h post partum and injected with oil or 100 μg oestradiol benzoate (OB). At 65 days of age, they were decapitated at various times and circadian plasma levels of prolactin, TSH and corticosterone were measured. Rats injected with OB had a significantly raised mean concentration of plasma prolactin, whereas levels of TSH and corticosterone did not differ from those of control rats. Plasma levels of corticosterone and prolactin were positively correlated both in oil-treated controls and oestrogenized rats. A small but not significant negative correlation existed between the levels of TSH and corticosterone in oil-treated control rats. This correlation became positive in rats neonatally injected with OB. Prolactin and TSH were positively correlated in oestrogenized rats but no correlation was found in control animals. It was possible to fit the diurnal variations of all hormones in oil-treated control and OB-injected rats to a significant sinusoidal curve. The acrophase for prolactin, but not for TSH and corticosterone, shifted significantly from 22·30 h in control rats to 14·69 h in oestrogenized rats. In oil-treated control rats, the acrophases of prolactin and corticosterone differed significantly by about 12 h from the TSH peak. In rats injected neonatally with OB, however, no difference between the acrophases of the hormones was seen.
It was, therefore, possible that the shift in prolactin release and the high plasma levels were both mediated by mechanisms which are common to TSH and prolactin and whose increased susceptibility is oestrogen-dependent. The role of this abnormal phasing relationship between prolactin, corticosterone and TSH which occurred in the oestrogenized rats is discussed in relation to the high incidence of various spontaneous or induced tumours which occur during later life in these rats.