Altered activation/detoxication enzymology following neonatal diethylstilbestrol treatment

The effects of neonatal exposure to diethylstilbestrol (DES) on hepatic activation/detoxication enzyme levels in the adult rat were investigated. Neonatal exposure of male rats to DES (DES males) decreased the endogenous levels of UDP-glucuronyltransferase as compared to control males. Female rats exposed neonatally to DES (DES females) had higher endogenous epoxide hydrolase and glutathione transferase activity levels than control females. Adult animals treated neonatally with DES also had altered metabolic potential following exposure to 3-methylcholanthrene and phenobarbital. The DES males treated in adulthood with 3-methylcholanthrene had higher benzo(a)pyrene hydroxylase activities and lower UDP-glucuronyltransferase activity levels than did control males treated in adulthood with 3-methylcholanthrene. The DES males exposed in adulthood to phenobarbital had reduced cytochrome P-450 and glutathione transferase activity levels as compared with respective controls. The DES females treated in adulthood with 3-methylcholanthrene had lower benzo(a)pyrene hydroxylase and epoxide hydrolase activity levels than control females receiving 3-methylcholanthrene. The DES females challenged in adulthood with phenobarbital also had decreased benzo(a)pyrene hydroxylase, epoxide hydrolase, UDP- glucuronyltransferase, and glutathione transferase activity levels as compared with respective controls. Our results demonstrated that neonatal exposure to DES changed the endogenous levels of specific hepatic enzymes and altered the metabolic response of these adult animals to a carcinogen and a drug.     

Effect of perinatal synthetic steroid hormone (allylestrenol, diethylstilbestrol) treatment (hormonal imprinting) on the bone mineralization of the adult male and female rat

Neonatal treatment with allylestrenol or diethylstilbestrol (DES) reduced the bone mineral content (BMC/bw) of the adult (four months old) female rats, without influencing bone mineral density (BMD/bw). In males these neonatal treatments elevated BMC and BMD alike. Ovariectomy alone decreased BMC and BMD alike; however the neonatal hormone treatments did not influence this reduced value. Ovariectomy of two months old animals increased body weight without the influence of neonatal hormone treatments. In adult males, the body weight was reduced significantly by neonatal DES and non-significantly by neonatal allylestrenol treatment. The experiments call attention to the possible human bone-effects of allylestrenol, which was used in the last decades as medication protecting endangered pregnancies.     

Hormonal imprinting by steroids: a single neonatal treatment with diethylstilbestrol or allylestrenol gives rise to a lasting decrease in the number of rat uterine receptors

Binding of hormone by the uterine receptors of 6 week old rats treated with diethylstilbestrol (DES) or allylestrenol (AE) in neonatal age differed considerably from the controls. Both pretreatments accounted for a decrease in the number of Type II binding sites for estradiol without altering receptor affinity. It follows that steroids, too, are able to induce a hormonal imprinting during the critical stage of receptor maturation.     

Effect of a single neonatal treatment with steroid hormone or steroid-like molecules on myocardial ouabain binding in the adult rat

A single neonatal treatment of rats with vitamin D3, gibberellin, allylestrenol or diethylstilbestrol (DES) influenced the ouabain binding capacity of myocardial Na, K-dependent ATP-ase. Of the active molecules tested, vitamin D3, DES and gibberellin had appreciable impact on myocardial ouabain receptors, enhancing and depressing their activity, respectively. The thymic dexamethasone and uterine estrogen receptors did not alter their binding capacity in response to neonatal exposure to vitamin D3 or gibberellin.     

Impact of a single neonatal gonadotropin (FSH + LH) or thyrotropin (TSH) treatment on the sexual behaviour of the adult male rat

A single gonadotropin (FSH + LH) treatment of neonatal male rats resulted in depression of sexual activity in adulthood. It appears that not only steroids, but also gonadotropins may alter adult sexual behaviour by a single neonatal exposure. The chemically related hormone thyrotropin (TSH) had a similar, but much less pronounced, effect on adult sexual activity.     

Transplacental estrogen responses in the fetal rat: increased uterine weight and ornithine decarboxylase activity

The synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE2), are more potent than 17 beta-estradiol (E2) in inducing uterine weight gain in the neonatal rat, due to the binding of E2 to serum alpha-fetoprotein (AFP). However, all three hormones are equipotent in inducing neonatal uterine ornithine decarboxylase (ODC) activity. The present study assessed estrogen potency in fetal rats. Pregnant CD rats were injected sc daily on gestation days (GD) 16-20 with DES, EE2, or E2 in sesame oil. Both DES and EE2, but not E2, significantly increased uterine weight at birth, to more than twice that of controls. In addition, implants which continuously release E2 only slightly increased uterine weight at birth. Alternatively, dams were given a single estrogen injection on GD 20 and were sacrificed at various times after injection. Peak fetal uterine ODC activity occurred at 6-8 hours after maternal injection for all three estrogens. E2 had a relative potency about tenfold less than either DES or EE2 in stimulating fetal ODC activity, in contrast to equal potencies of the three estrogens in the postnatal rat uterus. Similar patterns were found following direct fetal injection with E2 or DES. In summary, these data demonstrate a transplacental induction of fetal uterine ODC activity and uterine weight gain by both DES and EE2. In addition, the lack of correlation between these endpoints in response to E2 suggests that they may be useful as selective indicators of potential toxicity of both natural and synthetic estrogens.     

A comparison of the effects of castration and 6-methylene progesterone, a 5 alpha-reductase inhibitor, on the rat ventral prostate

6-Methylene progesterone (6MP) is an irreversible in vitro kcat inhibitor of rat prostate 5 alpha-reductase, the enzyme which converts testosterone (T) to dihydrotestosterone (DHT). Treatment of adult rats with 6MP or diethylstilbestrol (DES) decreased the weight of the ventral prostate (VP) by 45%, while castration reduced it by 86%. Histologically, the 6MP-treated VP were indistinguishable from those of controls, while the VP from DES-treated rats showed fibrous stromal hypertrophy as in castrated rats. The prostatic hydroxyproline content, an index of collagen levels, was enhanced by castration or DES, but was not significantly increased by 6MP. Within 2 days of 6MP treatment, the 5 alpha-reductase activity was reduced by 46% and ornithine decarboxylase (ODC) activity was lowered by 27%. During this time the prostatic acid phosphatase activity increased 42% and remained elevated with continued exposure to 6MP up to 13 days. The castration-induced involution of the VP was accompanied by a reduction in serum T and an increase in serum luteinizing hormone (LH). 6MP had no effect on T and LH serum levels but reduced the DHT content within the VP by 64%. Our results indicate that the structure and secretory acid phosphatase activity of the VP are less sensitive to changes in the ratio of T:DHT than is cell proliferation. Thus, the relative amounts of DHT and T within the VP may prove to be more significant than the absolute amount of either androgen in controlling prostate growth or its attendant neoplasms.     

The effect of lincomycin on the excretion of diethylstilbestrol and its uterotrophic action in rats.

The enterohepatic circulation of diethylstilbestrol (DES) has been shown to be extensive and to be dependent on enteric β-glucuronidase activity for release of absorbable DES from its nonabsorbable glucuronide excreted in bile. A regimen of the antibiotic lincomycin has been shown in rats to markedly reduce enteric β-glucuronidase activity, intestinal hydrolysis of C¹⁴-DES-glucuronide and absorption of radioactivity. Studies were therefore performed to determine if this lincomycin regimen, by reducing enterohepatic circulation of DES, would alter systemic effects of DES such as uterine weight gain in ovariectomized rats. The lincomycin regimen consisted of 25 mg twice daily by gastric intubation on days 1–4 and 500 mg/l in drinking water on days 1–7. Lincomycin-treated and control rats were injected s.c. with DES (1.6 or 5.0 μg/kg/day) on days 4–6 and sacrificed on day 7 for measurement of uterine weight; the injection on day 4 consisted on monoethyl-l-C¹⁴-DES. Lincomycin did not change the uterotrophic effect of DES. The regimen did, however, reduce the urinary excretion of radioactivity and increase the fecal excretion of glucuronide conjugates, consistent with reduced enterohepatic circulation of DES. In a separate study, bile from rats given DES s.c. was administered into the cecum of lincomycin-treated and control rats; whereas 31.8% of the cecal dose was excreted in the bile of controls, only 1.9% was excreted in lincomycin-treated rats, indicating the marked reduction of DES enterohepatic circulation produced by lincomycin. These findings suggest that the enterohepatic circulation of DES does not significantly contribute to its systemic effects.     

Expression of aquaporin 9 in rat liver and efferent ducts of the male reproductive system after neonatal diethylstilbestrol exposure.

Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from day 2 to day 20 postnatally at a dose of 4,8 microg/day, and AQP9 protein and mRNA were measured by immunoblotting and real-time PCR, respectively, along with immunohistochemistry. DES caused hepatic downregulation of AQP9 at both the protein and mRNA level; however, decreased AQP9 labeling was only observed in the periportal zone. In the ED, AQP9 protein expression was increased in the DES-treated animals by 300% that could be ascribed to a widening of the ED lumen, whereas no difference was observed in AQP9 mRNA expression. Immunohistochemical findings revealed that AQP9 expression was confined to the epithelial cells of the ED. In conclusion, neonatal DES exposure appears to upregulate AQP9 channels in the ED in male rats, whereas a downregulation in the hepatic expression was observed, particularly in the periacinous area.     

Long-term effects of postnatal exposure to diethylstilbestrol on uterine estrogen receptor and growth.

Diethylstilbestrol (DES) treatment of female rats on postnatal days (PND) 1-5 reduces uterine growth, estrogen receptor (ER) level and gland number by PND 25, while daily DES treatment on PND 1-25 increases uterine growth 4-fold, further reduces ER level and completely suppresses gland formation. We now report the persistence of these effects in adults. By PND 60, uterine weight was 70% of controls in rats injected with DES on PND 1-5 but only 10% of controls in rats injected PND 1-10 or longer. In fact, uterine weights were the same on PND 10 and 60. Uterine gland numbers were reduced to 30% of controls in all DES-treated rats regardless of exposure length; however, luminal and glandular epithelial cell heights were reduced to less than 50 and 70%, respectively, of controls when DES was given on PND 1-25 but not when given on PND 1-5. Ovariectomy 7 days prior to sacrifice on PND 60 reduced uterine weight in controls by 67% and in rats injected with DES on PND 1-5 by 53%, but had no effect in rats injected with DES on PND 1-10. DES exposure at either PND 1-5 or 1-10 lowered ER levels by 35-50% at both 60 and 90 days. Treatment with a high dose of estradiol (E2) 1 week before sacrifice significantly down-regulated ER to the same concentration in all treatment groups at PND 60 and 90. Following E2 treatment, all groups also showed increased uterine weight at PND 60 and 90. These data show there is a short period of development (PND 5-10) in which further DES exposure indirectly inhibits uterine growth.     

In vivo reopening of the neonatal ductus arteriosus by a prostanoid EP4-receptor agonist in the rat

Prostaglandin E1 is used to reopen the constricted ductus arteriosus in neonates with ductus-dependent circulation. To clarify possible prostanoid receptor agonists that can reopen the neonatal ductus with fewer side effects, we studied in vivo reopening of the neonatal ductus arteriosus by AE1-329, a prostanoid EP4-receptor agonist, in the rat. Neonatal rats were incubated at 33 degrees C. The inner diameter of the ductus was measured with a microscope and a micrometer following rapid whole-body freezing. Intraesophageal pressure was measured with a Millar micro-tip transducer. The ductus arteriosus constricted quickly after birth, and the inner diameter was 0.80 and 0.08 mm at 0 and 60 min after birth. PGE1 and AE1-329, injected subcutaneously at 60 min after birth, dilated the ductus dose-dependently. Thirty minutes after injection of 10 ng/g of PGE1 and AE1-329, the ductus diameter was 0.52 and 0.65 mm, respectively. The ductus-dilating effect of PGE1 was maximal at 15-30 min, and disappeared at 2 h. The ductus-dilating effect of AE1-329 was prolonged, the ductus was widely open at 6 h, and closed at 12 h after injection of 10 ng/g AE1-329. AE1-259-01 (EP2 agonist) (100 ng/g) did not dilate the neonatal ductus. Respiration was depressed by PGE1, but not by AE1-329. These results indicate the major role of EP4 in the neonatal ductus and that AE1-329, an EP4 agonist, can be used to dilate the neonatal constricted ductus without the side effects shown by EP3, including apnea.     

Neonatal estrogen exposure of male rats alters reproductive functions at adulthood

The effects of neonatal exposure to different doses of diethylstilbestrol (DES) on the reproductive functions of male rats at adulthood were evaluated. Sprague-Dawley rats (5-8/group) received sc injections of 25 microl olive oil containing DES (Sigma Chemical Co., St. Louis, MO) at a dose of 10 microg, 1 microg, 100 ng, 10 ng, or 1 ng per rat on alternate days from Postnatal Days 2-12. Control animals received olive oil only. All animals were allowed to develop until 83-91 days of age; however, when they were 70 to 80 days old, four male rats each from the 10 microg, 1 microg, 100 ng, and control groups were cohabited with untreated 60- to 70-day-old females (1:1) for 12 days. At the end of cohabitation, both mated and unmated male rats were weighed, and blood and tissue samples were collected and processed. Results revealed that although sperm motility patterns and sperm morphology were adversely affected in the 10- microg group, other reproductive parameters, including 1). daily sperm production (DSP)/testis; 2). absolute and relative weights of the testis, epididymis, and seminal vesicle; and 3). sperm numbers in both regions of the epididymis declined significantly in a dose-dependent manner in the 10- and 1- microg groups. Conversely, in the <1- microg groups, none of these parameters (except DSP/testis and weight of the epididymis in the 100-ng group, and sperm numbers in the epididymis of the 100- and 10-ng groups) was different from controls. Generally, plasma testosterone levels decreased in the 10- and 1- microg groups, FSH level increased in the 10-microg group, and prolactin and LH levels were unaltered. In the fertility study, although each male in the 1-microg, 100-ng, and control groups produced a copulatory plug and impregnated a female, none could do so in the 10-microg group. The mean number of pups per litter was reduced to eight in the 1-microg group, in contrast to 15 each in the 100-ng and control groups. In conclusion, exposure of neonatal male rats to DES altered sperm motility patterns, sperm fertility (as evident from the reduced number of pups in the 1-microg group), and sexual behavior (as evident from the absence of copulatory plugs in the 10-microg group) and reduced weights of reproductive organs, DSP/testis, and sperm numbers in the epididymis. Whether these alterations/reductions persist in older rats (6-8 mo of age) is under investigation.     

Hormonal imprinting and damages caused by fetal steroid treatment. Influence of fetal treatment with pregnancy-protecting steroids (allylestrenol, diethylstilbestrol) on the effect of gonadotropin administered to cockerels perinatally and at the age of six weeks

Single fetal (9th day) treatment with either diethylstilbestrol (DES) or allylestrenol (AE) caused a considerable decrease, both at the age of five days and six weeks, in the weight of the testicles and the diameter of the seminiferous cords, while the ratio of spermatogonia to primary spermatocytes increased. When measured either at the age of five days or six weeks, gonadotropin treatment [a combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH)], administered twice daily for three days after the hatching, led to an increase in the above-mentioned parameter and to a shift in the cell ratio towards the control value. However, the absolute value of the controls treated with FSH-LH was by far not reached. The effect of perinatal treatment could be detected even in adulthood, namely, at the age of five days the response capability was relatively weak in the cockerels treated with DES and AE, while high responsiveness was observed at the age of six weeks. In some cases the relative value of the increment exceeded even that of the control; however in absolute term it was well below the control. On the basis of these experiments it might be concluded that hormonal imprinting evoked by FSH-LH treatment also occurs in the gonad damaged by DES and AE. The setting in of imprinting ameliorates the damages caused by DES and AE and increases the response capability of the cells.     

ACE activity during the hypotension produced by standardized aqueous extract of Cecropia glaziovii Sneth: A comparative study to captopril effects in rats

To evaluate the effect of the standardized aqueous extract (AE) of Cecropia glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1) activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive control on the same animals. The effects on the blood pressure were recorded directly from the femoral artery (single dose), or indirectly by the tail cuff method (repeated doses) in conscious rats. The plasma ACE activity was determined spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The arterial blood pressure, heart rate and plasma ACE activity were not significantly modified within 24 h after a single dose administration of AE. Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and heart rate was increased by 10-20% from 30 min to 24 h after drug administration. ACE activity after captopril presented a dual response: an immediate inhibition peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To correlate the drug effects upon repeated administration of either compound, normotensive rats were separated in three groups: animals with high ACE (48.8+/-2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/-0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg after 14 days. The hypotension was reversed upon washout 60 days afterwards. Likely, repeated captopril administration decreased blood pressure by 20 mm Hg throughout treatment in all groups. After 30 days treatment with AE (0.5 g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group. After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h in all groups. It is concluded that the hypotension produced by prolonged treatment with AE of C. glaziovii is unrelated to ACE inhibition.     

Altered morphogenesis of the immature hamster uterus following neonatal exposure to diethylstilbestrol

Abstract. In previous studies, we found that a single neonatal exposure to diethylstilbestrol (DES) resulted in severe hyperplasia and a high incidence of endometrial adenocarcinoma in the uterus of adult hamsters. These observations prompted us to investigate the consequences of DES exposure on earlier stages of uterine morphogenesis. After neonates were treated within 6 h of birth (day 1) with 100 μg of DES or oil vehicle, uterine tissue morphometry plus cell labelling indices following in vivo pulse labeling with [³H]thymidine were determined on days 3–21 of life. The sequential findings were: (1) a precocious (day 3) burst of cellular proliferation throughout the uterus, (2) an early period (days 3–9) of hypertrophy and increased cell density in the luminal epithelium, (3) an extreme acceleration of uterine growth resulting in a persistent increase in total uterine mass (threefold enhancement on days 5–21), (4) precocious development of endometrial glands (day 9) that were sites of intense but transient proliferative activity, (5) a middle period (days 9–15) when the percentage of stromal cells engaged in proliferative activity was reduced, (6) a second wave (days 15–21) of enhanced proliferative activity in the luminal epithelium, and (7) later development (day 21) of reduced cell density in the uterine stroma, apparently due to increased intercellular collagen accumulation. These results support our working hypothesis that the acute uterotropic response to neonatal DES treatment initiates a change in the developing hamster uterus, and later estrogenic stimulation promotes neoplastic progression in the DES-altered adult organ, perhaps due to disruption of stromal-epithelial interactions.     

Diethylstilbestrol versus estradiol as neonatal disruptors of the hamster (Mesocricetus auratus) cervix

The synthetic estrogen diethylstilbestrol (DES) is an established, estrogenic endocrine disruptor (ED). The Syrian golden hamster (Mesocricetus auratus) offers some unique advantages as an experimental system to investigate the perinatal ED action of DES and other estrogenic EDs. Previous analyses regarding the consequences of neonatal administration (100 microg) of DES versus estradiol-17beta (E2) showed that DES had a more potent disruptive effect on morphogenesis and gene expression in the uterus, oviduct, and ovary as well as in the testis and male accessory organs. The objectives of the present study were to describe the histopathological consequences of the two neonatal treatment regimens in the hamster cervix and to compare them with our previous observations in the hamster uterus. As previously found in the hamster uterus, DES was more potent than E2 as a neonatal disruptor of the hamster cervix in prepubertal animals and in ovarian-intact adult animals. However, the cervix-versus-uterus scenario diverged in animals that were ovariectomized prepubertally and then chronically stimulated with natural estrogen (E2). We confirmed previous observations that neonatal exposure to DES, but not to E2, permanently alters estrogen responsiveness in the adult hamster uterus, but neither neonatal treatment regimen affected estrogen responsiveness in the adult hamster cervix. These results suggest that an unidentified ovarian factor influences the extent of neonatal DES-induced disruption of the cervix, but not of the uterus, in hamsters.     

Involvement of the Na+-independent Cl-/HCO3- exchange (AE) isoform in the compensation of myocardial Na+/H+ isoform 1 hyperactivity in spontaneously hypertensive rats

Enhanced activity of Na+/H+ isoform 1 (NHE-1) and the Na+-independent Cl-/HCO3- exchange (AE) is a feature of the hypertrophied myocardium in spontaneously hypertensive rats (SHR). The present study explored the possibility that sustained intracellular acidosis due to increased myocardial acid loading through AE causes NHE-1 enhancement. To this aim, SHR were treated for 2 weeks with a rabbit polyclonal antibody against an AE3 isoform that was recently developed and proven to have inhibitory effects on myocardial AE activity. We then compared the AE activity in the left ventricle papillary muscles isolated from untreated SHR with antiAE3-treated SHR; AE activity was measured in terms of the rate of intracellular pH recovery after an intracellular alkali load was introduced. AE activity was diminished by approximately 70% in SHR treated with the antiAE3 antibody, suggesting that the AE3 isoform is a major carrier of acid-equivalent influx in the hypertrophied myocardium. However, the antibody treatment failed to normalize NHE-1 activity that remained elevated in the myocardium of normotensive rats. The data therefore rule out the possibility that NHE-1 hyperactivity in hypertensive myocardium was due to sustained intracellular acidosis induced by increased AE activity that characterizes SHR myocardial tissue.     

Influence of prenatal steroid exposure on neonatal gonadotropin imprinting. Effect of single and combined hormone treatments on the chicken ovary

Chicken embryos treated with DES or AE at the 9th day of incubation showed postnatally an increase in ovarian mass, parenchymal zone thickness, follicle diameter and granulosa cell count. Perinatal gonadotropin treatment had a similar effect on these parameters in the control birds not receiving pretreatment, but had no influence on them in the birds pretreated with steroid. The tested ovarian parameters of the DES- and AE-pretreated birds still differed from the control at 6 weeks of age. Neonatal gonadotropin exposure induced imprinting in the birds not pretreated with steroid, to judge from an increased response (indicated by changed values of the tested parameters) to gonadotropin reexposure in adulthood. Similar, but considerably slighter changes were also shown by the steroid pretreated birds. It follows that in the birds prenatally exposed to AE or DES, supervening perinatal exposure to gonadotropin did not elicit greater changes than the prenatal exposure itself.     

Influence of a single treatment with vitamin E or K (hormonal imprinting) of neonatal rats on the sexual behavior of adults

The effect of a single neonatal treatment (imprinting) with vitamin E or vitamin K1 on the sexual activity of three-month old rats, was studied. In female animals vitamin E treatment significantly lowered the Meyerson index and lordosis quotient, among males there were significantly more inactive animals and no multiple ejaculations could be observed. Vitamin K1 treatment caused only slight changes in the same direction, in both sexes. Considering also earlier results concerning vitamin A and D neonatal treatments (alterations in receptor binding capacity, sex hormone levels and sexual behavior), and receptorial changes caused by neonatal vitamin E and K1 treatments, the present experiment also calls attention to the lifelong effects of perinatal treatment with lipid soluble vitamins.     

Impact of single neonatal serotonin treatment (hormonal imprinting) on the brain serotonin content and sexual behavior of adult rats

Hormonal imprinting takes place perinatally at the first encounter between the developing receptor and its target hormone. As a consequence of imprinting the receptor accomplishes its maturation and reaches the binding capacity characteristic to the adult age. In the excess of target hormone or presence of molecules similar to the target hormone, which are able to bind to the unmatured receptors, faulty imprinting develops with life-long consequences. At present, serotonin was given to neonatal rats and their sexual activity, brain serotonin level and steroid receptor's binding capacity was measured in adult age. Brain serotonin level was significantly reduced in male's striatum and parallel with this, male's sexual activity significantly increased. In other regions of the male brain (prefrontal cortex, hypothalamus, hippocampus) there was a statistically non-significant tendency for a decrease in serotonin level. No significant differences were detected in female brain values, and there was only slight change in female's sexual activity. There was also no change in the binding capacity of thymic glucocorticoid and uterine estrogen receptors. The experiments call attention to the possibility of perinatal imprinting by a neurotransmitter causing changes in brain neurotransmitter level for life, which is manifested in altered sexual activity.