Effects of adrenal steroids on Na transport in the lower intestine (Coprodeum) of the hen

Summary The influence of adrenal steroids on sodium transport in hen coprodeum was investigated by electrophysiological methods. Laying hens were maintained on low-NaCl diet (LS), or on high-NaCl diet (HS). HS hens were pretreated with aldosterone (128 g/kg) or dexamethasone (1 mg/kg) before experiment. A group of LS hens received spironolactone (70 or 160 mg/kg, for three days). The effects of these dietary and hormonal manipulations on the amiloride-sensitive part of the short-circuit current were examined. This part is in excellent agreement with the net Na flux, and therefore a direct electrical measurement for Na transport. After depolarizing the basolateral membrane potential with a high K concentration, the apical Na permeability and the intracellular Na activity were investigated by currentvoltage relations for the different experimental conditions.Plasma aldosterone concentrations (PA) were low in HS hens, dexamethasone-treated HS hens and spironolactonetreated LS hens (<70pm). In contrast LS hens and aldosteronetreated HS hens had a PA concentration of 596±70 and 583±172pm, respectively. LS diet (chronic stimulation) had the largest stimulatory effect on Na transport and apical Na permeability. Hormone-treated animals had three- to fourfold lower values. Spironolactone supply in LS hens decreased Na transport and apical Na permeability about 50%.The results provide evidence that both mineralo- and glucocorticoids stimulate Na transport in this tissue by increasing the apical Na permeability. Quantitative differences between acute and chronic stimulation reveal a secondary slower adaptation in apical membrane properties.     

Trigeminal nerve: the possible origin of substance p-nergic response in isolated rabbit iris sphincter muscle

We determined the effects of trigeminal nerve denervation on the noncholinergic, nonadrenergic response to electrical transmural stimulation of the isolated rabbit iris sphincter muscle. The left ophthalmic nerve (first branch of the trigeminal nerve) was cut at the intracranial, peripheral site of the trigeminal ganglion and five to ten days later, the iris sphincter muscle isolated from the left eye (operated side) was found to produce a fast cholinergic contraction in response to electrical transmural stimulation and there was no evidence of noncholinergic, nonadrenergic contractions. On the other hand, in the iris sphincter muscle isolated from the right eye (control side), electrical transmural stimulation produced both cholinergic and noncholinergic, nonadrenergic contractile responses. Capsaicin and bradykinin produced noncholinergic, nonadrenergic contractile responses in the muscle from the control side, while in the iris sphincter from the trigeminally denervated eye there was no such response to application of these drugs. Exogenous substance P (SP) and carbachol produced a strong contractile response in both the trigeminally innervated and denervated sphincter muscles. Somatostatin, vasoactive intestinal polypeptide (VIP) and enkephalin were without effects. These observations suggest that the noncholinergic, nonadrenergic responses to electrical transmural stimulation are derived from the trigeminal nerve and that the mediator involved is probably SP or a related peptide.     

Effect of electroacupunture and morphine on evoked potentials in the oral and caudal trigeminal nuclei of the cat

A comparative analysis of changes in the functional state of the oral and caudal trigeminal nuclei after electroacupuncture was undertaken in acute experiments on adult cats anesthetized with hexobarbital (50 mg/kg, intraperitoneally). Electroacupuncture was shown to inhibit evoked potentials arising in the caudal nucleus as a result of stimulation of the pulp, but not to change evoked potentials in response to stimulation of the mucosal surface of the lip. Electroacupuncture in the oral nucleus facilitated responses to both types of stimulation. Systemic injection of morphine (5 mg/kg, intravenously) gave similar results. It is suggested that the ventromedial part of the caudal nucleus facilitates the arrival of the diffuse component of the nociceptive signal in the nonspecific projection system, whereas the oral nucleus participates in conduction of information on possible injury to the structures of the oral cavity and realization of the necessary protective reactions.Central Research Institute of Reflex Therapy, Main Health Board, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 147–152, March–April, 1985.     

Modulating influence of the 2d somatosensory cortex of the cerebral cortex on the effects of electroacupuncture on the trigeminal nuclei

The effect of reversible functional inactivation of the second somatosensory cortex of the cerebral hemispheres on changes in the transmission of the afferent signals in the trigeminal nuclei after electroacupuncture was studied in acute experiments on adult cats anesthetized with hexenal (59 mg/kg i. p.). After functional inactivation of the second somatosensory cortex electroacupuncture failed to facilitate the evoked potentials in the oral trigeminal nucleus by stimulation of the tooth pulp and the lip of the mouth. In the caudal nucleus, the inhibitory effect of electroacupuncture on noxious stimulation decreased. The involvement of this brain cortex in the mechanisms of action of electroacupuncture on functionally different nuclei is discussed.     

Neurophysiological alterations following fluvalinate administration in mice.

Median lethal dose (LD50) of fluvalinate (Marvik 25EC) was 105 (94.6-116.5 mg/kg, ip) in albino mice. Gross observable signs were dose dependent and indicative of central and peripheral nervous system stimulation. Fluvalinate, at 10.5 and 21.0 mg/kg, ip doses in mice, facilitated maximal electroshock seizures, reduced reaction time in analgesic test and enhanced duration of ether anaesthesia. Acute and subacute (7 days) treatment at lower and higher doses enhanced pentobarbitone sleeping time. Acute and subacute treatment (7 days) with phenobarbitone (50 mg/kg, ip) prior to fluvalinate enhanced toxicity of fluvalinate.     

PE-11, a peptide derived from chromogranin B, in the rat eye

The aim of the study was to investigate the presence and distribution of PE-11, a peptide derived from chromogranin B, in the rat eye. For this purpose, newborn rats were injected with a single dosage of 50 mg/kg capsaicin subcutaneously under the neck fold and after three months, particular eye tissues were dissected and the concentration of PE-11-like immunoreactivity was determined by radioimmunoassay. Furthermore, PE-11-like immunoreactivities were characterized in an extract of the rat eye by reversed phase HPLC. Then, the distribution pattern of PE-11 was investigated in the rat eye and rat trigeminal ganglion by immunofluorescence. As a result, PE-11 was present in each tissue of the rat eye and capsaicin pretreatment led to a 88.05% (±7.07) and a 64.26% (±14.17) decrease of the levels of PE-11 in the cornea and choroid/sclera, respectively, and to a complete loss in the iris/ciliary body complex. Approximately 70% of immunoreactivities detected by the PE-11 antiserum have been found to represent authentic PE-11. Sparse nerve fibers were visualized in the corneal and uveal stroma, surrounding blood vessels at the limbus, ciliary body and choroid and in association with the dilator and sphincter muscle. Furthermore, immunoreactivity was present in the corneal endothelium. In the retina and optic nerve, glia was labeled. In the rat trigeminal ganglion, PE-11-immunoreactivity was visualized in small and medium sized ganglion cells with a diameter of up to 30 μm. In conclusion, there is unequivocal evidence that PE-11 is a constituent of capsaicin-sensitive sensory neurons innervating the rat eye and the distribution pattern is typically peptidergic in the peripheral innervation but in the retina completely atypical for neuropeptides and unique.     

Effect of imbrimycin on the body of animals]

Toxicity of imbrimycin administered orally and its local irritating effect was studied experimentally. Imbrimycin was diluted with flagosol for decreasing its local irritating effect on the mucosa of the eye conjunctiva and vagina of rabbits. Administration of imbrimycin suspension to albino rats in doses of 10 and 50 mg/kg for 14 days had no effect on the body weight, liver antitoxic function and pathomorphological indices. Oral administration of the drug to dogs in a dose of 10 mg/kg caused a decrease in the body weight, vomiting and diarrhea, had no effect on the dog blood picture and induced no pathomorphological changes in the inner organs. The local irritating effect of imbrimycin was found to be equal to that of azalomycin F. Flagosol significantly decreased the irritating effect of imbrimycin on the eye conjunctiva and the vagina mucosa.     

Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100mg/kg bw, administered intraperitoneally 30min prior to 9.5Gy whole-body gamma-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50mg/kg bw) in mice irradiated with 15Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25mg/kg bw.     

The mechanism of the intranasal action of dermorphin in representatives of 2 classes of vertebrates]

It has been shown that endogenous opioid dermorphin induces effective analgesia after intranasal injection to fish (0.02-0.20 mg/kg) and rats (0.005 mg/kg). Maintenance of dermorphin analgesia after olfactory and trigeminal denervation indicates that the analgetic effect is not realized via the olfactory receptors or free terminals of the trigeminal nerve.     

Evaluation of oral administration of cortisol and metyrapone: the effects on serum cortisol in rainbow trout (Salmo gairdneri)

The effect of manipulating dietary levels of cortisol and metyrapone on peripheral concentrations of serum cortisol was examined in rainbow trout, Salmo gairdneri. Fish were fed 0, 10, 20, 30, 40 or 50 mg/kg body weight/day of metyrapone or cortisol for 7 days. All levels of cortisol tested increased peripheral levels of serum cortisol. Feeding a level of 30-40 mg/kg body weight/day of metyrapone depressed serum cortisol. We describe, herein, a noninvasive technique for suppression or stimulation of serum cortisol in rainbow trout.     

Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit

Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.     

Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100 mg/kg bw, administered intraperitoneally 30 min prior to 9.5 Gy whole-body γ-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50 mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100 mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50 mg/kg bw) in mice irradiated with 15 Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50 mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100 mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25 mg/kg bw.     

Photoperiodic adjustments in immune function protect Siberian hamsters from lethal endotoxemia

Seasonal changes in day length enhance or suppress components of immune function in individuals of several mammalian species. Siberian hamsters (Phodopus sungorus) exhibit multiple changes in neuroendocrine, reproductive, and immune function after exposure to short days. The manner in which these changes are integrated into the host response to pathogens is not well understood. The present experiments tested the hypothesis that short-day changes in immune function alter the pathogenesis of septic shock and survival after challenge with endotoxin. Male and female Siberian hamsters raised in long-day photoperiods were transferred as adults to short days or remained in their natal photoperiod. Six to 8 weeks later, hamsters were injected i.p. with 0, 1, 2.5, 10, 25, or 50 mg/kg bacterial lipopolysaccharide (LPS) (the biologically active constituent of endotoxin), and survival was monitored for 96 h. Short days significantly improved survival of male hamsters treated with 10 or 25 mg/kg LPS and improved survival in females treated with 50 mg/kg LPS. Transfer from long to short days shifted the LD50 in males by approximately 90%, from 5.3 to 9.9 mg/kg, and in females from 11.1 to 15.0 mg/kg (+35%). Long-day females were more resistant than were males to lethal endotoxemia. In vitro production of the proinflammatory cytokine TNFalpha in response to LPS stimulation was significantly lower in macrophages extracted from short-day relative to long-day hamsters, as were circulating concentrations of TNFalpha in vivo after i.p. administration of LPS, suggesting that diminished cytokine responses to LPS in short days may mitigate the lethality of endotoxemia. Adaptation to short days induces changes in immune parameters that affect survival in the face of immune challenges.     

Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats

Background

In our present study, we studied the role of demyelination of the trigeminal nerve root in the development of prolonged nociceptive behavior in the trigeminal territory.

Results

Under anesthesia, the Sprague-Dawley rats were mounted onto a stereotaxic frame and 3 ??L of lysophosphatidic acid (LPA, 1 nmol) was injected into the trigeminal nerve root to produce demyelination. This treatment decreased the air-puff thresholds, persisted until postoperative day 130, and then returned to the preoperative levels 160 days after LPA injection. The LPA-treated rats also showed a significant hyper-responsiveness to pin-prick stimulation. We further investigated the antinociceptive and neuroprotective effects of progesterone in rats undergoing demyelination of the trigeminal nerve root. Progesterone (8, 16 mg/kg/day) was administered subcutaneously, beginning on the operative day, for five consecutive days in the LPA-treated rats. Treatment with progesterone produced significant early anti-allodynic effects and delayed prolonged anti-allodynic effects. The expression of protein zero (P0) and peripheral myelin protein 22 (PMP22) were significantly down-regulated in the trigeminal nerve root on postoperative day 5 following LPA injection. This down-regulation of the P0 and PMP22 levels was blocked by progesterone treatment.

Conclusions

These results suggest that progesterone produces antinociceptive effects through neuroprotective action in animals with LPA-induced trigeminal neuropathic pain. Moreover, progesterone has potential utility as a novel therapy for trigeminal neuropathic pain relief at an appropriate managed dose and is therefore a possible future treatment strategy for improving the recovery from injury.     

Biochemical and pharmacological activities of SSR 146977, a new potent nonpeptide tachykinin NK3 receptor antagonist

SSR 146977 is a potent and selective antagonist of the tachykinin NK3 receptor. In Chinese hamster ovary cells expressing the human tachykinin NK3 receptor, SSR 146977 inhibited the binding of radioactive neurokinin B to NK3 receptors (Ki = 0.26 nM), senktide (10 nM) induced inositol monophosphate formation (IC50 = 7.8-13 nM), and intracellular calcium mobilization (IC50 = 10 nM). It antagonized [MePhe7]neurokinin B induced contractions of guinea pig ileum (pA2 = 9.07). Senktide (30 nM) induced firing rate increase of noradrenergic neurons in the guinea pig locus coeruleus and dopaminergic neurons in the guinea pig substantia nigra was also blocked by SSR 146977 (50 and 100 nM, respectively). In vivo, in the respiratory system, SSR 146977 inhibited bronchial hyperresponsiveness to acetylcholine, bronchial microvascular permeability hypersensitivity to histamine (doses of 0.1-1 mg/kg i.p.), and cough (doses of 0.03-1 mg/kg i.p.) provoked by citric acid in guinea pigs. In the central nervous system, SSR 146977 inhibited turning behaviour (ID50 = 0.2 mg/kg i.p. and 0.4 mg/kg p.o.) and prevented the decrease of locomotor activity (10 and 30 mg/kg i.p) mediated by the stimulation of NK3 receptors in gerbils. In guinea pigs, SSR 146977 antagonized senktide-induced acetylcholine release in the hippocampus (0.3 and 1 mg/kg i.p) and norepinephrine release in the prefrontal cortex (0.3 mg/kg i.p.). It also prevented haloperidol-induced increase of the number of spontaneously active dopamine A10 neurons (1 and 3 mg/kg i.p.).     

Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate dehydrogenase concentration in the testis

Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, testicular histopathology (qualitative histopathology, seminiferous tubular diameter and epithelial height), and intra-testicular levels of testosterone and lactate dehydrogenase were assessed. Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day 14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's post hoc test). The sperm count was decreased on all sampling days except at 5 and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35 (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21, at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05-0.001). Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial sloughing was seen on days 14-35 and other histopathological changes observed were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7, at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated. The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50-100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and 35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate dehydrogenase concentration increased at all dose-levels up to day 35, but without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose-response of dacarbazine on any parameters tested. The sperm count (except on day 7-positive correlation; Pearson product moment correlation) or sperm motility did not have any relation but increase in abnormal sperms showed negative correlation with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count was in negative correlation on days 14 and 35, and increase in abnormal sperms showed positive correlation on day 35 with increase in LDH level. Finally, the decrease in sperm motility had no correlation with increase in abnormal sperm shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis.     

Effects of capsaicin and nitric oxide synthase inhibitor on increase in cerebral blood flow induced by sensory and parasympathetic nerve stimulation in the rat.

Effects of electrical stimulation of the nerve bundles including sensory and parasympathetic nerves innervating cerebral arteries on cerebral blood flow (CBF) and mean arterial blood pressure (MABP) were investigated with a laser-Doppler flowmeter and a blood pressure monitoring system in anesthetized rats pretreated with and without capsaicin. The electrode was hooked on the nerve bundles including the distal nasociliary nerve from trigeminal nerve and parasympathetic nerve fibers from sphenopalatine ganglion. In control rats, the nerve stimulation for 30 s increased CBF in the ipsilateral side and MABP. Hexamethonium attenuated the increase in CBF and abolished that in MABP. Under treatment with hexamethonium, N(G)-nitro-L-arginine (L-NNA, 1 mg/kg) significantly attenuated the stimulation-induced increase in CBF, which was restored by the addition of L-arginine. Although the dose of L-NNA was raised up to 10 mg/kg, the stimulation-induced increase in CBF was not further inhibited and was never abolished. In capsaicin-pretreated rats, magnitudes of the stimulation-induced increases in CBF and MABP were lower than those in control rats. Hexamethonium attenuated the increase in CBF and abolished that in MABP. Under treatment with hexamethonium, L-NNA abolished the stimulation-induced increase in CBF in capsaicin-pretreated rats. In conclusion, nitric oxide released from parasympathetic nerves and neuropeptide(s) released antidromically from sensory nerves may be responsible for the increase in CBF in the rat. The afferent impulses by nerve stimulation may stimulate the trigeminal nerve and lead to the rapid increase in MABP, which partly contributes to the increase in CBF.     

Action of an ovulation stimulator on the genital function of the female rat]

Effect of cyclofenil on genital function implied organs, is studied in cyclic female rats injected s. cut: 0.5, 5 or 50 mg/kg/day, during 12 days. The treatment increases pituitary, adrenal and uterine weights, decreases ovarian weight, adrenal and ovarien cholesterol. These data suggest that cyclofenil acts directly or undirectly at different levels of hypothalamo-pituitary-genital axis with central inhibition and light peripheral stimulation.     

Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats.

Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.     

Antiestrogenic and antitumor properties of the new triphenylethylene derivative toremifene in the rat

The effects of toremifene, a new triphenylethylene derivative, on the uterus and DMBA-induced mammary tumors in rats were compared to tamoxifen. The ability of toremifene to compete with [3H]estradiol for cytoplasmic estrogen receptor from rat uterus was similar to tamoxifen, the IC50 being 26 and 23 microM respectively. In immature intact rats the two compounds, administered orally for three consecutive days, had similar intrinsic partial estrogenic efficacy, at 50 mg/kg, about 40% of that of estradiol benzoate (EB). However, at doses less than or equal to 10 mg/kg, the estrogenic effect of toremifene was seen at doses about 40 times higher than that of tamoxifen. The two compounds, administered together with a standard dose of EB, expressed the same maximal antiestrogenic efficacy (about 65% inhibition) at 50 mg/kg. However, the minimal effective antiestrogenic dose of toremifene was about 10 times that of tamoxifen and the ratio between antiestrogenic/estrogenic properties was favourable to toremifene. The duration of the antiestrogenic (antiuterotrophic) effect of a single oral dose (10 mg/kg) of the two compounds proved similar: at least 4 days in intact rats and 3 days in ovariectomized rats. In DMBA-induced tumor bearing rats toremifene was administered p.o., 6 times/week for 4 weeks at 0.08, 0.4, 2, 10 and 50 mg/kg. It was effective at the doses of 2, 10 and 50 mg/kg, inducing 39, 35 and 46% tumor regressions. The activity of toremifene at the minimal effective dose of 2 mg/kg was then compared with that of tamoxifen given at the same dose level. The compounds had comparable activity (47 vs 44% tumor regressions).