The site of action of ‘chlormadinone acetate’ (6‐chloro‐Δ⁶‐dehydro‐17α‐acetoxyprogesterone) in blocking ovulation in the mated rabbit

Abstract

SUMMARY1. In a study of the site of action of a steroid in current use for contraceptive purposes (6-chloro-A6-dehydro-17az-acetoxyprogesterone; 'chlormadinone acetate'), the ovarian responses [secretion rate of 20a-hydroxypregn-4-en-3-one (20 x-OH), and the occurrence of ovulation] were observed in control oestrous rabbits and in rabbits following mating, injection of luteinizing hormone, and after electrical stimulation of the median eminence.2. Chlormadinone acetate pretreatment (0 5 mg i.v.) did not lower significantly the secretion of 20 ax-OH in otherwise untreated oestrous rabbits.3. Chlormadinone acetate, given 24 hr before mating, prevented the rise in 20ac-OH that would otherwise have occurred, and also blocked the ovulation response following mating.4. Chlormadinone acetate pretreatment did not prevent the ovarian responses to administration of luteinizing hormone.5. Chlormadinone acetate pretreatment did not prevent the ovarian responses to electrical stimulation of the median eminence of the tuber cinereum of the hypothalamus.6. The conclusion is drawn that the chlormadinone acetate block of the ovarian responses following mating is at a site in the central nervous system located above the median eminence.

The action of chlormadinone acetate (6‐chloro‐Δ6‐dehydro‐17α‐acetoxyprogesterone) upon experimentally induced ovulation in the rabbit

“…Exley et al (1968) confirmed these results using doses of 0 5 mg chlormadinone acetate injected intravenously. It was found by this latter group of workers that such administration of chlormadinone acetate does not abolish the ovarian response to electrical stimulation of the median eminence.…”

“…A possible explanation of the results of Exley et al (1968) and of the present work is as follows. Intravenous injection of chlormadinone acetate in female rabbits may result, during the next 24 hr, in a reduced secretion of FSH.…”

“…It is established that 24 hr after administration of chlormadinone acetate some 50 % of normal female rabbits show a lack of sexual responsiveness to the male (Kincl & Dorfman, 1963 a, b;Exley et al 1968), probably due to diminished ovarian secretion of oestrogens. In this connexion the results referred to above of Hilliard et at.…”

“…In a recent paper (Exley, Gellert, Harris & Nadler, 1968) the possible site of action of steroidal compounds in inhibiting ovulation in the mated rabbit was discussed. In that study it was reported that a particular pro-G. W. HARRIS AND R. M. SHERRATT gestational compound (6-chloro-A6-dehydro-17a-acetoxyprogesterone, chlormadinone acetate) failed to block the ovarian response to electrical stimulation of the median eminence of the tuber cinereum, although a consistent block in the ovarian response was observed to follow mating.…”

A study of the parameters of electrical stimulation of unmyelinated fibres in the pituitary stalk

“…secretion of luteinizing hormone, in rabbits by hypothalamic stimulation with a sine-wave current of 50 c/s (i.e. a pulse or cycle duration of 20 msec and 0-25-1-0 mA peak-to-peak current strength) has been reported recently (Exley, Gellert, Harris & Nadler, 1968). Ovulation has been produced in rats by septal and hypothalamic stimulation with biphasic square-wave pulses by Everett (1965) and G. W. Harris & K. B. Ruf (in preparation) (with pulse parameters 30 c/s, 2 msec pulse duration and 1-0 mA peak-to-peak current strength).…”