Considerably less progesterone was needed to facilitate than was required to inhibit sexual receptivity induced by oestradiol benzoate (OB) and progesterone in the ovariectomized rat. Inhibition of sexual receptivity occurred if progesterone was given at the time of OB treatment (concurrent inhibition). If progesterone was given 42 h after the OB treatment it first acted to facilitate the behaviour and then to inhibit the response to renewed progesterone treatment 24 h later (sequential inhibition). Both concurrent and sequential inhibition of sexual receptivity by progesterone could be reversed by increasing the dose of progesterone before behavioural testing. Sexual receptivity could be induced in the pseudopregnant rat by using a low dose of OB (2 μg) in combination with a very high dose of progesterone (50 mg). Sexual receptivity induced in ovariectomized rats by injection of a single large dose of OB was unaffected by progesterone treatment in both the concurrent and sequential paradigm. Concurrent and sequential inhibition of sexual behaviour by antioestrogen (nitromophene monocitrate, CI-628) treatment could not be reversed by increasing the dose of progesterone before testing. The behavioural response to OB treatment in combination with progesterone and OB treatment alone was markedly inhibited by CI-628 treatment. It is suggested that prior treatment with progesterone raises the threshold of the behavioural response to subsequent progesterone treatment. It is also suggested that the inhibitory effect of progesterone on sexual behaviour cannot only be accounted for by the previously suggested antioestrogenic effect of progesterone.
S. HANSEN and P. SÖDERSTEN
P. SÖDERSTEN and S. HANSEN
Castration of rats on the day of birth abolished the capacity to ejaculate and reduced the capacity to show intromissions in response to testosterone propionate (TP) treatment in adults. Day 10 castrated rats treated daily with oil or day 0 castrated rats treated daily with testosterone benzoate (TB) during the first 10 days of life achieved intromissions and ejaculation after TP treatment in adulthood. Treatment of day 0 castrated rats with a high dose of TB during the first 10 days of life enhanced their capacity to ejaculate in response to TP treatment in adulthood to a level above that of day 10 castrated rats given oil in infancy and similarly treated with TP as adults.
Castration on the day of birth greatly reduced the increase in penis weight and the development of cornified papillae on the glans penis which were seen in day 10 castrated rats after TP treatment in adulthood. These peripheral effects of neonatal testicular secretions are reversed by neonatal treatment of day 0 castrated rats with TB.
Daily treatment of day 0 castrated rats with dihydrotestosterone benzoate (DHTB) during the first 10 days of life facilitated the increase in weight of the penis and the development of cornified papillae on the glans penis but did not enhance the capacity to ejaculate in response to TP treatment in adulthood. Daily treatment of day 0 castrated rats with oestradiol benzoate (OB) during the first 10 days of life facilitated ejaculation without increasing penis sensitivity to TP in adulthood. Combined treatment of the neonate with OB and DHTB was no more effective in facilitating ejaculation in the adult than was OB alone. Neonatal treatment with OB was considerably more potent than neonatal treatment with TB in enhancing ejaculatory behaviour in adulthood.
It is suggested that both the inhibition of the development of lordosis behaviour and the facilitation of the development of mounting behaviour by testicular secretions in newborn rats may be dependent upon, but variously sensitive to, the amount of oestradiol formed in the brain from testosterone in the blood during the first 10 days of life.
P. SÖDERSTEN and S. HANSEN
The ability of cyclic female rats to show sexual receptivity 24 h after an injection of 2 μg oestradiol benzoate (OB) was lost 24 h after ovariectomy. Exposure of cyclic rats to anti-oestrogen (nitromophene monocitrate) implants 24 h before ovariectomy and OB treatment prevented the latter from inducing sexual receptivity within 24 h of administration. Treatment of ovariectomized rats with constant release implants filled with an oil solution of 15 μg oestradiol/ml had no behavioural effect in itself, but prepared the rats to show lordosis 24 h after administration of OB. Progesterone treatment (4 mg) induced sexual behaviour in cyclic rats on days other than that of the oestrous cycle when the rats are normally receptive. Evidence is presented that a lower level of oestradiol stimulation than that present during pro-oestrus was needed for the induction of sexual receptivity in ovariectomized rats. It is suggested that the low basal level of oestradiol which was present throughout the oestrous cycle was necessary for the induction of sexual receptivity and that an increase in oestradiol stimulation served to increase the behavioural sensitivity to progesterone.
S. HANSEN and P. SÖDERSTEN
Ovariectomized rats, pre-implanted with elastomer capsules containing oestradiol, became sexually receptive after exposure to progesterone (implanted in elastomer capsules) for 4–6 h. Implantation of progesterone capsules facilitated receptivity in oestradiol-implanted rats independently of both previous exposure to progesterone implants and the presence of progesterone at the time of implantation.
The duration of sexual receptivity in ovariectomized rats implanted with oestradiol and progesterone capsules was dependent upon the length of both the oestradiol and progesterone capsules, but the decline in sexual behaviour of receptive rats was independent of the continued presence of either oestradiol or progesterone. Repeated implantation of progesterone capsules at 6 hourly intervals prevented the decline of sexual receptivity.
P. SÖDERSTEN and S. HANSEN
Intact 4-day cyclic rats showed sexual receptivity 24 h after an injection of oestradiol benzoate (OB) on any day of the cycle except on the second day after the display of spontaneous oestrus. Ovariectomy at the time of OB treatment abolished the behavioural response, but receptivity was restored by progesterone. Progesterone treatment early on the day of behavioural oestrus advanced the display of receptivity but did not affect the time at which oestrus ended. Repeated treatment of sexually receptive rats with progesterone did not affect the duration of oestrus. These results show that sexual receptivity in the intact rat cannot occur in the absence of oestradiol and progesterone. The results further suggest that progesterone may not be associated with the mechanisms terminating behavioural oestrus in rats. Treatment with OB on the day of oestrus can prolong the duration of receptivity but only at a higher dosage than that needed for induction of receptivity.
A. M. Vinggaard and H. S. Hansen
In the present study we report that bradykinin stimulated phospholipase D activity in rat Leydig cells. Bradykinin added for 8 min stimulated choline formation in a dose-dependent manner and, in the presence of ethanol, bradykinin (100 nmol/l) stimulated transphosphatidylation by phospholipase D resulting in the formation of phosphatidylethanol. This stimulation was abolished after down-regulation of protein kinase C by long-term pretreatment for 22 h with phorbol 12-myristate 13-acetate (PMA). The stimulation of phospholipase D by the simultaneous addition for 8 min of maximum concentrations of PMA and vasopressin (AVP), PMA and bradykinin, or AVP and bradykinin produced no additive phosphatidylethanol or choline response, suggesting that AVP, bradykinin and PMA stimulated phospholipase D-catalysed phosphatidylcholine hydrolysis by a similar protein kinase C-dependent mechanism. Furthermore, LH (10 ng/ml), insulin (500 nmol/l), GH (100 ng/ml), interleukin-1β (5 U/ml) and platelet-activating factor (200 nmol/l) were found not to activate phospholipase D, whereas the Ca2+ ionophore A23187 (10 μmol/l) stimulated phosphatidylethanol formation, suggesting that Ca2+ might be a regulator of phospholipase D in Leydig cells.
Journal of Endocrinology (1993) 136, 119–126
P. SÖDERSTEN, S. HANSEN and B. SREBRO
Male rats were treated daily with oil or 100 μg of the antioestrogen, ethamoxytriphetol (MER-25), for the first 10 days of life and, when adult, lesions were made in the suprachiasmatic nuclei (SCN) of the hypothalamus or control lesions were made above the SCN and the rats were tested for sexual behaviour. Treatment with MER-25 enhanced the daily rhythmicity in both mounting and lordosis behaviour and SCN lesions disrupted these behavioural rhythms and the rhythm in the mounting behaviour of oil-treated rats. Rats treated with MER-25 and with SCN lesions showed high levels of mounting and lordosis behaviour throughout the light: darkness cycle. These results support the hypothesis that sexual differentiation by perinatal androgen stimulation uncouples the central rhythm generator from the neural substrates of sexual behaviour in rats.
P. Södersten, S. Hansen and P. Eneroth
Injection of 2·5 mg of the dopamine receptor antagonist domperidone raised serum prolactin concentrations within 3 h and high prolactin levels were maintained for 12 h in ovariectomized rats pretreated with 2 μg oestradiol benzoate (OB). This dose of domperidone stimulated the display of sexual behaviour in ovariectomized OB-treated rats within 3 h of administration. The behavioural effect of domperidone, but not its effect on serum prolactin concentrations, was blocked by adrenalectomy. Daily treatment with domperidone had no inhibitory effect on the subsequent induction of sexual behaviour by OB and progesterone in ovariectomized rats. A slight facilitation of the behaviour was noticed in OB-treated rats given daily domperidone injections, but this effect was cancelled by adrenalectomy. The results suggest that an acute increase in serum prolactin levels has no effect on the induction of sexual behaviour by OB in itself, but can stimulate the secretion of an adrenal product, perhaps progesterone, which facilitates the behaviour. Similarly, constant high levels of prolactin by themselves have no effect on the subsequent induction of sexual behaviour by OB and progesterone.
P. SÖDERSTEN, P. ENEROTH and S. HANSEN
Constant-release implants filled with oestradiol-17β induced sexual receptivity in ovariectomized rats in response to progesterone treatment if they were implanted 32 h before behavioural testing. A 20 h period of exposure to oestradiol, by implantation 32 h before testing and removal of the implants 20 h later, was sufficient for induction of the behaviour. The exposure time necessary for behavioural responses could be further reduced to two 4 h periods, between 32 and 28 h and between 16 and 12 h, before testing. Serum levels of oestradiol were raised within 1 h of oestradiol implantation and declined rapidly after implant removal. A single injection of oestradiol benzoate was much more potent than a single injection of oestradiol in inducing sexual receptivity in ovariectomized rats, but this difference in potency was reversed if two appropriately timed injections were given. Oestrone- or oestriol-filled implants were relatively ineffective in inducing sexual receptivity. It is suggested that oestradiol has to be present at crucial time points to prepare an ovariectomized rat to respond behaviourally to progesterone treatment and that oestradiol is the principal oestrogen in the stimulation of sexual behaviour in female rats.
P. Södersten, S. Hansen and P. Eneroth
Treatment with oestradiol benzoate (OB; 2–250 μg) and progesterone (0·5–25 mg) failed to induce sexual behaviour in lactating rats 6 days after parturition. Removal of pups permitted the induction of sexual behaviour by OB and progesterone and the inhibitory effect of the presence of pups was proportional to the number present. Ovariectomy of lactating rats or reduction of serum prolactin levels in intact lactating rats by daily treatment with the dopamine receptor agonist bromocriptine (0·5 mg/day) permitted the induction of sexual behaviour despite the presence of suckling pups. Removal of pups from lactating rats and subsequent maintenance of high prolactin levels by daily treatment with the dopamine receptor antagonist domperidone (2·5 mg/day) maintained the state of refractoriness to the behavioural effects of OB and progesterone provided that the ovaries remained in situ. Inhibition of sexual behaviour in lactating rats could be maintained after ovariectomy by implantation of progesterone-filled, but not androgen-filled implants at the time of ovariectomy. Removal of the pups or reduction of prolactin levels by bromocriptine treatment permitted the induction of sexual behaviour by OB in ovariectomized progesterone-implanted lactating rats. Inhibition of the behaviour in ovariectomized progesterone-implanted lactating rats could be maintained after pup removal by daily domperidone treatment. Continuously raised serum progesterone or prolactin levels have no effect on the induction of sexual behaviour in female rats but the present data suggest that during lactation progesterone and prolactin act in synergy to inhibit the behaviour.