The Effects of Oestrogen: Androgen Interaction on the Reticulo-Endothelial System and Reproductive Tract

Abstract

1) Oestrone, oestriol, 17\g=b\-oestradiol,ethinyloestradiol, oestradiol monobenzoate, diethylstilboestrol, 4-hydroxy-\g=a\,\g=b\-diethyldibenzyl(HDB), dienoestrol, hexoestrol, triphenylethylene and tri-p-anisylchloroethylene (TACE) stimulated the reticulo-endothelial system (RES) in intact male and in ovariectomized female mice.(2) Testosterone propionate inhibited the vaginal smear response to all the above oestrogenic compounds. It also inhibited the RE stimulation produced by oestrone, oestriol, ethinyloestradiol, oestradiol monobenzoate, triphenylethylene and TACE but had no effect on RE stimulation by diethylstilboestrol, HDB, dienoestrol or hexoestrol; it markedly potentiated the stimulant effect of 17\g=b\-oestradiol on the RES.(3) The effect on the RES of oestrogen : androgen interaction does not appear to be dependent on the type of androgen used.

The Effect of Various Anti-Oestrogenic Compounds on the Reticulo-Endothelial System and Reproductive Tract in the Ovariectomized Mouse

“…Oestriol and 17a-ethynyl-19-nortestosterone have no effect on the RE stimulation produced by 17/?-oestradiol, but both compounds inhibit the RE stimulant effect of diethylstil¬ boestrol. Testosterone and progesterone did not inhibit the RE stimulant effects of 17/?-oestradiol and diethylstilboestrol-in fact, testosterone potentiated the stimulant effect of 17/?-oestradiol on the RES which confirms previous findings (Nicol et al , 1966. MER-25 depressed the RE stimulant effects of both 17^-oestradiol and diethylstilboestrol to the level of the untreated controls.…”

“…The effects of oestrogen : androgen interaction on the RES have already been described (Nicol et al 1966). It was shown that testosterone has no effect on the RE stimulation produced by the stilbene-type of oestrogen, but strongly potentiates the RE-stimulant effect of 17/?-oestradiol.…”

“…MER-25 structurally resembles the phenylstilbenes, yet despite its uterotrophic effect it has no stimulant action on the RES, although the related phenylstilbenes, triphenylethylene and tri-p-anisylchlorethylene (TACE), stimulate the RES (Nicol et al 1966). It is widely accepted that triphenylethylene and TACE are pro-oestrogens which undergo metabolic changes in the liver before being able to act (Emmens, 1942;Segaloff, 1944), and their molecular structure is responsible for their action as pro-oestrogens.…”

“…It appears likely that MER-25 also induces a utero¬ trophic response by acting as a pro-oestrogen. It is surprising that MER-25 inhibits the RE stimulant action of 17/?-oestradiol and diethylstilboestrol since testosterone inhibits the RE-stimulant effect of triphenylethylene and TACE (Nicol et al 1966) (which are structurally related to MER-25) but not the RE-stimulant action of 17/?-oestradiol and diethylstilboestrol. For the other anti-oestrogenic compounds used the results do not appear to be related to the degree of saturation of the central carbon skeleton, since ring A of oestriol is aromatic and ring A of the other compounds has a single double bond between C-4 and C-5.…”

“…The oestrogens selected as stimulants of the RES and reproductive tract in this investigation were 17/?-oestradiol and diethylstilboestrol since we have previously shown that they interact in the same manner with testosterone on the RES (Nicol et al 1966). Testosterone, progesterone, oestriol, 17a-ethynyl-19-nortestosterone and l-(^-2-diethylaminoethoxyphenyl)-1 -phenyl -2 -p -methoxyphenylethanol (MER-25) were selected as representative of the various groups of anti-oestrogenic compounds : androgens, progestins, 'impeded' oestrogens, nor-steroids and non-steroids.…”