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Castration, dopamine and food choice: a cost/benefit test in male hamsters.

Testosterone is essential for copulation, and contributes to sexual motivation. In addition, castrated males are fatter and less active, suggesting that androgens may play a role in non-sexual behaviors, including food-related responses. To test this hypothesis, male hamsters were trained with a cost/benefit test, which compares operant responding for more-preferred food versus ad libitum consumption of lab chow. Males were tested before and after castration. The effect of the dopamine antagonist, haloperidol, on instrumental responses in intact and castrated males was also determined. Food-deprived hamsters responded vigorously for 45 mg Bio-Serv pellets in daily 30-min tests (665 presses, 6.0+/-0.9 g). When lab chow was available, males continued to respond for pellets (3.6+/-0.6 g) over chow ad libitum (1.2+/-0.3 g). Dopamine is central to this response because haloperidol (1.0 mg/kg i.p.) reversed food intake (pellets: 0.5+/-0.1 g; chow 2.0+/-0.5 g). Castration had no effect on operant responding for pellets alone (6.6+/-0.7 g). When chow was present, castrates consumed an even greater proportion of their total food intake as pellets [6.0+/-0.4 g pellets (92%), 1.6+/-0.5 g chow (8%), vs. 75 and 25%, respectively, for intact males]. This is contrary to our original hypothesis. In addition, castration did not change the effects of haloperidol on food intake: (0.4+/-0.1 g pellets; 1.6+/-0.5 g chow). These results support previous findings in rats that dopamine affects response allocation in a cost/benefit test. However, they do not support the hypothesis that testosterone modifies the allocation of food-related responses.

Animals↗

Effects of castration and androgen replacement on tumour growth of human hepatocellular carcinoma in nude mice.

BACKGROUND/AIMS: Previous clinical investigations suggest that androgen and its receptor (AR) may play an important role in the growth of hepatocellular carcinoma. Few studies are available concerning the effect of androgen manipulation on the growth of AR-positive hepatocellular carcinoma in vivo. METHODS: AR-positive (SM10) and AR-negative (SM2) sublines derived from a human hepatocellular carcinoma line KYN-1 were implanted subcutaneously in the lower abdomen of nude mice. The tumour size and expression of proliferating cell nuclear antigen and Lewis Y antigen were examined in intact males, castrated males, intact females, and castrated males with androgen replacement. AR of the tumour was measured with binding assay, ultracentrifugation, and Western blotting. RESULTS: The growth of SM10 was significantly better in intact males and castrated males with 5a-dihydrotestosterone injection than in intact females and castrated males. Castration did not suppress the growth of SM2. The tumour AR level was reduced by castration but maintained by the hormone substitution. Although proliferating cell nuclear antigen expression was closely associated with tumour growth, Lewis Y antigen expression did not differ among the groups. CONCLUSIONS: These data may indicate that this hepatocellular carcinoma subline (SM10) is androgen-responsive and that androgen ablation can cause the inhibition of the tumour growth, which might be due to decreased proliferative and not increased apoptotic activities. In addition, such androgen-stimulated tumour growth seems to be mediated through AR.

Androgens↗

Castration increases pulsatile luteinizing hormone release, but fails to diminish mounting behavior in sexually experienced bulls.

We tested the hypothesis that mounting and chemoinvestigatory behaviors are testosterone-dependent in bulls. Eighteen bulls were divided into three treatment groups: intact (I), castrated (C) and castrated+testosterone (T). Sexual behaviors of all bulls were tested with an unrestrained receptive female 1 week prior to and weekly for 4 weeks after castration. Mounts with intromissions, aborted mounts and flehmen responses were quantified for each test period. In addition, patterns of LH and testosterone secretion were assessed at these times. Neither mounts with intromissions nor aborted mounts were affected by treatment. In contrast, numbers of flehmen responses were lower in C bulls than in the other groups following castration. Before castration, concentrations of LH were not different among groups and LH pulse frequency was approximately one pulse per hour. Castration resulted in a 2-fold increase in mean concentrations of LH and a 6-fold increase in LH pulse frequency. Neither mean concentration of LH nor LH pulse frequency changed in I or T bulls. The data fail to support the hypothesis that mounting behavior is T-dependent, but supports the hypothesis that this steroid hormone regulates flehmen behavior in sexually experienced bulls.

Animals↗

Effects of castration on alpha 1-adrenoceptor subtypes in the rat aorta.

The expression of alpha 1-adrenoceptor subtypes in several tissues is regulated by gonadal hormones. In this study, we investigated whether castration regulates the alpha 1-adrenoceptor subtypes mediating the contractions of the aorta from male rats to noradrenaline. Noradrenaline induced similar concentration-dependent contractions in the aorta from control and castrated rats. Treatment of the aorta from both control and castrated rats with the alpha 1B/alpha 1D-adrenoceptor alkylating agent chloroethylclonidine resulted in approximately 1600-fold rightward shift in the concentration-response curves to noradrenaline. The pA2 values found for WB 4101, benoxathian (alpha 1A-selective) and BMY 7378 (alpha 1D-selective) indicate that alpha 1D-adrenoceptors are involved in the contractions of the aorta from control and castrated rats to noradrenaline. However, there was a 15-fold difference between the pKB estimated through the lowest effective concentrations of the alpha 1A-adrenoceptor selective antagonist 5-methyl-urapidil in the aorta from control and castrated rats. The pKB estimated in aorta from control rats is consistent with the interaction with alpha 1D-adrenoceptors (7.58 +/- 0.06), while that calculated in organs from control rats is consistent with alpha 1A-adrenoceptors (8.76 +/- 0.09). These results suggest that castration induces plasticity in the alpha 1-adrenoceptor subtypes involved in the contractions of the aorta to noradrenaline.

Adrenergic alpha-Agonists↗

Association of castration-dependent early induction of c-myc expression with a cell proliferation of the ventral prostate gland in rat.

The protooncogene c-myc is known to be associated with both cell proliferation and apoptosis. The possible cellular affects of castration on the ventral prostate gland of rat as well as the relationship to a castration induced c-myc expression were examined. Levels of c-myc mRNA in the ventral prostate gland peaked at 6 h (early induction) and 48 h (late induction) after castration, respectively. Castration-induced DNA fragmentation was not observed at an early induction of c-myc mRNA. DNA fragmentation appeared to be testosterone-dependent. On the other hand, cellular DNA synthesis measured by [3H]thymidine uptake in the ventral prostate gland was increased to maximum at 6 h after castration. These results suggest that an early induction of c-myc mRNA in ventral prostate gland after castration is closely associated with cell proliferation of the gland.

Animals↗

Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate.

1. The prostate function is regulated by androgens and alpha-adrenergic activity. Clinically, antiandrogens and/or alpha(1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha(1)-adrenoceptor, the characteristics and expression of alpha(1)-adrenoceptors were examined in castrated rats. 2. Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [(3)H]-prazosin and phenoxybenzamine (3 - 300 nM) were used for inhibition assay, receptor characterization and partial alkylation of alpha-adrenoceptor, respectively. The mRNA content of three subtypes of alpha-adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT - PCR). 3. Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the affinity or density of alpha(1)-adrenoceptor. Escalating alkylation of the alpha(1)-adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT - PCR study confirmed the expression of three types of alpha(1)-adrenoceptor, alpha(1a), alpha(1b) and alpha(1d)-adrenoceptors, in intact rat prostate, and revealed that alpha(1a)-adrenoceptor, but not alpha(1b) or alpha(1d)-adrenoceptors, was down-regulated in castrates. 4. The results show that androgen deprivation suppressed alpha(1)-adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the alpha(1a)-adreneroceptor population expressed in intact rat prostate.

Adrenergic alpha-1 Receptor Antagonists↗

The evaluation of androgen circulating levels following castration in adult male rats.

In the present study dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) plasma levels were determined in adult male rats five days, seven weeks and eleven weeks after orchiectomy and confronted, respectively, with rats 60 days old which were sacrificed 5 days, 7 weeks and 11 weeks after the sham-operation for orchiectomy. It was revealed that five days after castration A, T and DHT were decreased with respect to sham-operated rats. Seven and eleven weeks after orchiectomy only T remained lower. In all three groups of castrated animals the A/T ratio resulted augmented whereas T/DHT ratio resulted lower with respect to the sham-operated animals. Five days after castration DHEA plasma concentration was positively correlated to A levels and both androgens resulted negatively correlated to T plasma levels. Seven weeks after bilateral orchiectomy an inverse correlation appeared between DHEA/A ratio and T. This emphasizes the role of DHEA and A in maintaining testosterone circulating levels. Seven and eleven weeks following castration the A/T ratio was negatively related to the T/DHT ratio, indicating that A contributes to DHT plasma levels. In the second part of our study the effect of sex steroid administration was evaluated 7 weeks after castration. A linear correlation between DHEA and T circulating levels was obtained following the administration of T while treatment with oestradiol caused a significant increase of the DHEA/A ratio. The castrated animals that received DHT presented lower T circulating levels while the A/T ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Changes in bone mineral density differ between gonadotrophin-releasing hormone analogue- and surgically castrated men with prostate cancer--a prospective, controlled, parallel-group study.

OBJECTIVE: The effects of surgical and medical castration on bone mineral density (BMD) were compared in men receiving castration therapy as a result of prostate cancer. A control group of men of similar age was also included in the study. MATERIAL AND METHODS: A total of 28 men with prostatic cancer who had been selected to undergo medical or surgical castration and 10 healthy men with benign urological disorders were followed from baseline observations and BMD was assessed at 3, 6, 12 and 36 months. Serum hormone levels were also assessed. RESULTS: Orchidectomy and treatment with gonadotrophin-releasing hormone (GnRH) analogues caused an expected rapid decrease in serum testosterone levels, with no difference between these two groups. The mean loss of BMD in the femoral neck measured by means of dual-energy X-ray absorptiometry in surgically castrated men and GnRH-treated men was 0.037 g/cm2 (4.53%; SEM 0.013 g/cm2; p = 0.010) and 0.027 g/cm2 (3.18%; SEM 0.014 g/cm2; p = 0.119), respectively at 12 months, while the controls gained 0.017 g/cm2 (1.26%; SEM 0.013 g/cm2; p = 0.195). In the heel, surgically castrated men lost 9.04% of BMD (p < 0.001), the GnRH-treated men lost 3.58% (p = NS) and the controls gained 1.26% (p = NS). CONCLUSION: We found a more pronounced decrease in BMD in men with metastatic prostate cancer who were treated with surgical castration than in those who were treated with GnRH analogues.

Aged↗

Cortisol responses of young lambs to castration and tailing using different methods.

Lambs at 4-5 weeks of age were studied during the first 4 hours after castration and/or tailing using three methods in various commonly used combinations. The methods were cutting with a knife, application of constricting rubber rings and using a heated docking iron (tailing only). The integrated cortisol response (area under the cortisol curve) was determined for each lamb during the first 4 hours after treatment and was considered to reflect the overall magnitude of the lamb's acute distress response. On that basis, cut lambs (tailing only, castration only, castration plus tailing) experienced more distress than any other groups. Also the distress response (indicated by elevated plasma cortisol concentrations) lasted longer than 4 hours in cut lambs, unlike all other groups. The use of rings apparently caused similar distress when lambs were castrated only, were castrated plus tailed, or were short-scrotumed (testes pressed against the abdominal wall by a distally located scrotal ring) plus tailed. The magnitudes of distress apparently caused by tailing alone with a ring or a docking iron were similar and were lower than the distress caused by any other castration and/or tailing procedure. It is concluded that acute distress responses to these husbandry procedures would be minimised in lambs of this age if rings and/or a docking iron were used in preference to a knife.

Journal Article↗

Induction of apoptosis by castration in epithelium of the mouse seminal vesicles.

Castration on days 0, 5, 10, 20, 40, and 60 caused increases in an apoptotic index (% of apoptotic cells) in seminal vesicle (SV) epithelium, peaking 1-3 days after castration. The peak apoptotic indices after castration on days 0, 5, 10, and 20 were significantly lower than peak apoptotic indices observed after castration on days 40 and 60. DNA extracted from mouse SVs 2 days after castration on days 0, 5, 10, and 60 showed a ladder pattern on agarose gel electrophoresis. The secretion of androgen by testes was confirmed by the growth retardation of the SVs after castration on days 0, 5, 10, and 20. It would appear that a proportion of SV epithelial cells dependent on testicular androgens for survival is smaller before day 20 than after day 20.

Animals↗

Effects of intermittent pulsatile infusion of luteinizing hormone-releasing hormone on dihydrotestosterone-suppressed gonadotropin secretion in castrate rams.

The feedback effects of dihydrotestosterone (DHT) on gonadotropin secretion in rams were investigated using DHT-implanted castrate rams (wethers) infused with intermittent pulsatile luteinizing hormone-releasing hormone (LHRH) for 14 days. Castration, as anticipated, reduced both serum testosterone and DHT but elevated serum LH and follicle-stimulating hormone (FSH). Dihydrotestosterone implants raised serum DHT in wethers to intact ram levels and blocked the LH and FSH response to castration. The secretory profile of these individuals failed to show an endogenous LH pulse during any of the scheduled blood sampling periods, but a small LH pulse was observed following a 5-ng/kg LHRH challenge injection. Dihydrotestosterone-implanted wethers given repeated LHRH injections beginning at the time of castration increased serum FSH and yielded LH pulses that were temporally coupled to exogenous LHRH administration. While the frequency of these secretory episodes was comparable to that observed for castrates, amplitudes of the induced LH pulses were blunted relative to those observed for similarly infused, testosterone-implanted castrates. Dihydrotestosterone was also shown to inhibit LH and FSH secretion and serum testosterone concentrations in intact rams. In summary, it appears that DHT may normally participate in feedback regulation of LH and FSH secretion in rams. These data suggest androgen feedback is regulated by deceleration of the hypothalamic LHRH pulse generator and direct actions at the level of the adenohypophysis.

Animals↗

Calcium-dependent and calcium-independent gelatinolytic proteinase activities of the rat ventral prostate and its secretion: characterization and effect of castration and testosterone treatment.

Calcium-dependent and calcium-independent proteinase activities were detected in extracts of rat ventral prostate and its secretion by use of gelatin-containing SDS-PAGE zymography. Ca(2+)-independent proteinase activities of 22, 26, and 73-79 kDa and Ca(2+)-dependent activities of 58, 63, and 66 kDa were found in the adult gland. The 26- (most intense activity of gland) and 22-kDa activities were present in secretion and were not expressed in the undifferentiated gland of the 10-day-old animal. The Ca(2+)-dependent activities were also present in the secretion, where the 63-kDa form was more prominently expressed than the 58- and 66-kDa bands. The Ca(2+)-dependent and Ca(2+)-independent proteinase activities both responded to a broad range of pH values in the incubation media. The 73-79-kDa Ca(2+)-independent activities were sensitive to benzamidine and the Ca(2+)-dependent activities were inhibited by EDTA and EGTA. Both Ca(2+)-dependent and Ca(2+)-independent proteinase activities responded to androgenic manipulations. Castration was followed by the appearance of a 35-kDa Ca(2+)-independent proteinase (at 2 days) and a 43-kDa Ca(2+)-dependent proteinase (at 4 days). In the Ca(2+)-independent proteinase group, the 73-79-kDa activities were increased somewhat and the 22- and 26-kDa activities decreased after castration. The Ca(2+)-dependent proteinases of 58, 63, and 66 kDa increased in activity with castration, but activity of the 58-kDa form decreased again at 7 days after castration. Treatment of animals upon castration for 4 days with hydrocortisone prevented these changes in proteinase activities whereas treatment with actinomycin D or tranexamic acid did not. Testosterone propionate replacement therapy of rats castrated for 16 days stimulated the activities of the 22- and 26-kDa and 73-79-kDa Ca(2+)-independent and the 58- and 63-kDa Ca(2+)-dependent proteinases with 4 days of therapy. The activities of the 35-kDa Ca(2+)-independent and the 43-kDa Ca(2+)-dependent proteinases were repressed with 8 days of testosterone treatment. Thus, individual proteinases show differential changes in activity during development and in response to androgenic manipulation: this suggests that in addition to proteinases which are secreted, others may be involved in intracellular functions or in mediating tissue organization changes.

Animals↗

Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys.

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.

Androstenedione↗

Visually stimulated erection in castrated men.

Sexual interest and activity decrease following castration. We determined by objective criteria the erectile status of 16 men who were sexually active before castration for prostatic cancer. Castration was achieved by orchiectomy or hormonal manipulation. Patients answered a questionnaire regarding the medical status and erectile function before and after castration, and the blood level of testosterone was assessed. During viewing of an erotic videotape penile circumference and erection quality were monitored. Four patients (25%) achieved functional erection. Mean serum free testosterone levels in men who achieved erection were 1.125 +/- 0.362 pg./ml. (standard deviation) and 0.628 +/- 0.098 pg./ml. in those not achieving functional erection (p < 0.001). No statistically significant difference was noted in age, interval since castration, co-morbidity score or method of castration between the men who did and did not achieve erection.

Aged↗

Castration reduces blood pressure and autonomic venous tone in male spontaneously hypertensive rats.

OBJECTIVE: The development of arterial hypertension is sexually dimorphic. Venous tone is elevated in the spontaneously hypertensive rat model of hypertension. This study tested the hypothesis that endogenous androgens exacerbate venous tone in the developmental stages of spontaneous hypertension. METHODS: Male spontaneously hypertensive rats (SHRs) were subjected to sham operation, castration or castration + testosterone treatment. Ten-week-old SHR rats were instrumented for the measurement of arterial and venous pressure. A balloon catheter was advanced into the right atrium. Mean circulatory filling pressure (MCFP), an index of venous tone, was calculated. Mean arterial pressure (MAP) and MCFP were recorded from conscious rats. Postsynaptic adrenergic responsiveness was assessed by constructing cumulative dose-response curves to norepinephrine (NE). Baseline values and responsiveness to NE were obtained before and after autonomic blockade. RESULTS: MAP and MCFP were significantly reduced in castrated (MAP, 130 +/- 4 mmHg; MCFP, 5.5 +/- 0.2 mmHg) versus sham-operated SHRs (MAP, 149 +/- 5 mmHg; MCFP, 6.7 +/- 0.3 mmHg) or castrated + testosterone-treated SHRs (MAP, 145 +/- 6 mmHg; MCFP, 7.1 +/- 0.4 mmHg). Ganglion blockade abolished these differences in MAP and MCFP. Infusion of NE caused dose-dependent increases in MAP and MCFP. The MAP responses in castrated SHRs were displaced to the right of those for sham and castrated + testosterone-treated SHRs. This was not evident in the venous circulation, where there were no marked differences in the NE dose-MCFP response curves. CONCLUSION: Accordingly we conclude that endogenous male sex steroids contribute to the elevated arterial and venous pressures observed in the SHR.

Animals↗

Castration inhibits glomerular hypertrophy and proteinuria in uninephrectomized male rats.

Renal mass reduction may lead to glomerular hypertrophy, proteinuria and focal glomerulosclerosis (FGS) in humans and rats. In humans and rats, females are less susceptible than males to these phenomena. This study was undertaken to evaluate the effect of male rat castration on the pathogenesis of proteinuria and FGS. Urinary protein was measured in 60-day-old male and female rats. Uninephrectomy was performed in all rats, and castration in half of the males. After 180 days, proteinuria, glomerular filtration rate (GFR) and blood biochemistry were determined. Kidneys were resected, weighed and subjected to morphologic studies. Following uninephrectomy, male rats developed severe proteinuria: 132.3 +/- 40.9 mg 24 h-1, most of which was accounted for by an albuminuria of 70.9 +/- 19.3 mg 24 h-1. In contrast, protein excretion in female and castrated male rats remained within normal limits: 8.0 +/- 1.8 and 4.2 +/- 0.5 mg 24 h-1, respectively. Mean glomerular volume in male rats was 1.18 +/- 0.08 x 10(6) microns3; much higher than in female rats, 0.84 +/- 0.04 x 10(6) micron3, and castrated male rats, 0.87 +/- 0.03 x 10(6) micron3 (P less than 0.005). On light and electron microscopy, glomeruli of female and castrated male rats were completely normal. In contrast, in four of seven male rats, mild glomerular changes were observed. They consisted mainly of mesangial expansion, electron-dense deposits and collapse of capillary loops. These data suggest that castration confers protection against the development of glomerular hypertrophy and proteinuria in uninephrectomized male rats. Endogenous testosterone may be associated with this development.

Animals↗

Influence of castration on isoprenaline-induced amylase release in parotid gland from male rats.

The purpose of this study was to determine the influence of testosterone, the male sex hormone, on beta-adrenergic agonist-induced amylase secretion from rat parotid glands. Isoprenaline (isoproterenol)-induced amylase secretion was measured in vitro from the parotid glands of control and castrated rats with and without testosterone replacement. The isoprenaline-induced amylase release was reduced in parotid glands from castrated rats compared to controls. The reduction of amylase release by isoprenaline in parotid glands of castrated rats, could be reversed by administration of testosterone. Furthermore, beta-adrenergic receptor density and the level of isoprenaline-evoked cAMP in parotid glands from castrated rats was lower compared to intact rats. Using SQ-22536 (an adenylyl cyclase inhibitor), dibutyryl cAMP (a cAMP analogue) and verapamil (a calcium channel blocker), we conclude that the impairment of amylase release from parotid glands after castration was not related to either adenylyl cyclase activity or cAMP accumulation. Amylase release from the parotid glands of castrated rats appears to be mediated by an increase in calcium ion influx.

Adrenergic beta-Agonists↗

Hypothalamic LHRH concentration decreases in intact but increases in castrated rats in constant light.

In order to evaluate the effects of environmental lighting on the hypothalamic secretion of luteinizing hormone-releasing hormone (LHRH), intact and castrated male Wistar rats were kept either in periodic (LD) or in constant light (LL) for 1 week, and the hypothalamic LHRH concentration was measured by radioimmunoassay. In the intact rats the LHRH concentration was lower in constant than in periodic light (30 +/- 3 vs 61 +/- 3 pg mg-1, P less than 0.05), whereas in the castrated rats it was higher (16 +/- 2 vs 5 +/- 1 pg mg-1, P less than 0.05). The intact and castrated rats received melatonin (50 micrograms) or saline injections daily at either 09.00 h or 16.00 h in LD and LL for 1 week. In intact or castrated rats the melatonin injections were not able to prevent the change of hypothalamic LHRH in constant light. In castrated rats testosterone (125 or 250 micrograms) had no effect on the LHRH concentration under either lighting condition. The present results suggest that constant light reduces the synthesis of hypothalamic LHRH in intact rats but increases it in castrated rats. These effects of constant light do not appear to be related to melatonin.

Animals↗