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T. J. ROBINSON and W. M. BRANDER

Summary.

The activities of six oestrogenic substances were compared when given as a single injection, intravenously (i/v) or intramuscularly (i/m), to spayed progesterone-primed ewes. The following values for the ED50 for oestrous behaviour, with associated 95% fiducial limits, were obtained:

Oestradiol-17β (i/v) 16 —, 25 — 39; (i/m) 3 — 7 — 16

Oestradiol benzoate (i/v) 30 — 45 — 69; (i/m) 5 — 11 — 23

Oestrone (i/v) 48 — 96 — 194; (i/m) No data

Diethylstilboestrol (i/v) 6 — 10 — 18; (i/m) 6 — 10 — 18

Hexoestrol (i/v) 46 — 103 — 234; (i/m) 46 — 103 — 234

Methylethylstilboestrol (i/v) ∞ — ; (i/m) 130 — 279 — 600

They fell into three groups, with the following i/v : i/m ratios: natural oestrogens; oestradiol- 17β, oestradiol benzoate, 4 : 1: synthetic oestrogens; diethylstilboestrol and hexoestrol, 1 : 1 : pro-oestrogen; methylethylstilboestrol, ∞ : 1.

True oestrogens are presumed to accumulate in the reacting tissues with variable efficiencies. Pro-oestrogens, given i/v, are probably ineffective because they are not converted to oestrogens in a manner or at a rate suitable for such accumulation.

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W. M. BRANDER and T. J. ROBINSON

Summary.

Osmotic injection pumps have been used to determine time-dose relationships in the response of spayed progesterone-primed ewes to oestrogen. Oestradiol benzoate (odb) has been injected in propylene glycol directly into the jugular vein over the range 0 to 32 hr. No relationship could be demonstrated between time and total dose in the behavioural and vaginal response, but there was a significant total-dose/response effect. The ED50 of odb for behavioural oestrus was 23 ug. No dose-response effect could be demonstrated for vaginal changes.

The pumps delivered at a linear rate (b = 0·029, ±0·003; y = 0·029 —0·053, where y = volume in millilitres and x = time in hours), over the time range studied, but were highly variable.

It is concluded that the reacting tissues, neural and vaginal, are able to absorb and utilize odb with an almost equal degree of efficiency if it is given either as a single intravenous injection or as a continuous infusion over many hours.