Neonatal exposure to Δ9-tetrahydrocannabinol enhances sexual responses in the adult male mouse

1986 ◽  
Vol 110 (3) ◽  
pp. 517-523 ◽  
Author(s):  
P. Shrenker ◽  
R. Stegar ◽  
A. Bartke

ABSTRACT From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 μl sesame oil, 0·5 mg tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol (Δ9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 μl oil. Additionally, the pups were given 20 μl oil, 10 μg testosterone or 20 μg testosterone in 20 μl oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone-filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0·5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed. J. Endocr. (1986) 110, 517–523

1985 ◽  
Vol 105 (2) ◽  
pp. 175-181 ◽  
Author(s):  
K. L. Goodrowe ◽  
P. K. Chakrabortyt ◽  
D. E. Wildt

ABSTRACT To determine the influence of exogenous LH-releasing hormone (LHRH) on serum LH and testosterone, ten adult male domestic cats received three treatments on a rotating schedule at 10-day intervals as follows: (I) 0·1 ml saline i.m. (control); (II) 10 μg LHRH i.m., single injection; (III) 10 μg LHRH i.m., two injections given at a 2-h interval. Serial blood samples collected over a 360-min interval were analysed by radioimmunoassay for LH and testosterone. Although baseline serum LH values in saline-treated animals (treatment I) varied markedly among individual cats (2·2–29·2 μg/l), there was no evidence of pulsatile LH release or alterations in testosterone over time within individual males. In treatment II, the single injection of LHRH induced a rapid rise in mean serum LH within 30 min in all cats (mean peak, 88·2 ±9·8 μg/l), which returned to baseline by 120 min after LHRH. Mean testosterone increased within 30 min in this group (from 6·03 ±2·18 to 18·55 ±3·36 nmol/l), peaked at the 60-min collection (19·76 ± 2·77 nmol/l) and returned to baseline by the 150-min sample. After treatment III, serum LH peaked at 131·6±13·6μg/l within 30 min of the initial LHRH injection. A second injection of LHRH produced another LH surge within 30 min, but in all cats this second response was of a lower magnitude (mean peak, 69·0±14·5μg/l) and shorter duration (P<0·05). The second LHRH injection sustained peripheral testosterone levels for approximately 1 additional h. The increase in testosterone response was negatively correlated with pretreatment serum testosterone concentrations in both treatment groups (treatment II, r = −0·46; treatment III, r = −0·72). These results which provide an endocrinological data base for the male domestic cat: (1) demonstrate the acute sensitivity of the male pituitary-gonadal axis to a single injection of LHRH; (2) indicate that an additional LHRH challenge within 2 h results in a more attenuated LH surge, suggesting pituitary refractoriness to repeated LHRH administration; (3) suggest that gonadal sensitivity to LHRH administration is influenced by circulating testosterone. J. Endocr. (1985) 105, 175–181


1993 ◽  
Vol 137 (2) ◽  
pp. 247-NP ◽  
Author(s):  
H. F. Urbanski ◽  
M. M. Fahy ◽  
P. M. Collins

ABSTRACT The influence of excitatory amino acids (EAAs) on reproductive neuroendocrine function was investigated in adult male Syrian hamsters of the LSH/Ss Lak strain. Before the study, the animals were maintained in a sexually regressed condition, under short days (SD) and subsequently were either transferred to long days (LD) or kept under SD, for a further 4 weeks. In the former group, photostimulation produced a predictable elevation in the hypophysial contents and serum concentrations of FSH and LH. This was accompanied by an increase in testicular size, an elevation in serum testosterone levels and an increase in spermatogenic activity; the SD hamsters remained sexually quiescent throughout the study. In contrast, SD hamsters that were given daily injections of the EAA agonist, N-methyl-d,l-aspartate (NMA: 50 mg/kg body weight, s.c.), showed stimulatory responses that were generally even more pronounced than those shown by the LD group. Surprisingly, an identical NMA treatment paradigm failed to cause a similar activation of the reproductive axis in LD hamsters that were given daily afternoon injections of melatonin (25 μg, s.c), even though the inhibitory effect of this melatonin treatment is generally regarded as being comparable with that produced by exposure to SD. Although EAAs can acutely stimulate the neurocircuitry that controls LH-releasing hormone secretion, the present findings suggest that EAAs might also exert a long-term stimulatory action by acting further upstream in the photoneuroendocrine pathway. Journal of Endocrinology (1993) 137, 247–252


1999 ◽  
Vol 87 (6) ◽  
pp. 2274-2283 ◽  
Author(s):  
Gregory A. Brown ◽  
Matthew D. Vukovich ◽  
Rick L. Sharp ◽  
Tracy A. Reifenrath ◽  
Kerry A. Parsons ◽  
...  

This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 ± 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min ( P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 ± 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo ( n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly ( P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly ( P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.


2004 ◽  
Vol 25 (6) ◽  
pp. 1339-1354 ◽  
Author(s):  
Warrick McKinon ◽  
Craig Hartford ◽  
Luca Di Zio ◽  
Johan van Schalkwyk ◽  
Demetri Veliotes ◽  
...  
Keyword(s):  

1980 ◽  
Vol 93 (3) ◽  
pp. 287-293 ◽  
Author(s):  
E. Jean Wickings ◽  
E. Nieschlag

Abstract. Adult male rhesus monkeys are aggressive animals and very difficult to handle. Hence experimental manipulations necessarily involve the use of restraint procedures, either chemical or physical, which may influence endocrine functions. Therefore, the effects of ketamine anaesthesia on basal hormone levels and on the pituitary response to LRH and TRH were investigated in 4 adult male rhesus monkeys. Values were compared to those obtained from the same animals restrained in primate chairs for approximately 48 h, a procedure to which they had been accustomed to over the preceding 6 months. Serum cortisol levels under anaesthesia were at all times lower than in conscious monkeys, but increased after 2 h to values twice as high as measured initially. Serum testosterone concentrations were not significantly different on the two occasions, but levels under anaesthesia were slightly higher initially than in the conscious monkeys, and decreased gradually over the 3 h test period. Initial prolactin levels were lower in the anaesthetized monkeys, and increased 2–3-fold after 90 min; values at 3 h were not significantly different from those in conscious monkeys. Intravenous TRH elicited a similar response in prolactin on both occasions, maximum values occurring after 15–30 min and returning to basal levels after 3 h. The maximum values attained and the area under the response curves were higher under anaesthesia. LRH stimulation resulted in a 15- and 30-fold increase in serum levels of biologically active LH, with and without anaesthesia, respectively. Basal levels were not significantly different on the two occasions. The area under the LH response curve was higher in 3 of the 4 monkeys without anaesthesia. The extent to which results in conscious monkeys are affected by stress is difficult to assess. Since neither handling technique allows for the collection of 'true' basal data, it is paramount to standardize and define the conditions under which experiments, and even routine blood sampling, are performed in male rhesus monkeys.


1987 ◽  
Vol 115 (4) ◽  
pp. 478-482 ◽  
Author(s):  
J. Roffi ◽  
F. Chami ◽  
P. Corbier ◽  
D. A. Edwards

Abstract. In the neonatal male rat, a rapid and transient increase in serum testosterone occurs about 2 h after birth. This post-partum testosterone surge (PPTS) has been implicated in the masculinization and defeminization of the central nervous system. The present study shows that environmental temperature can have a profound influence on the PPTS. Male rats were delivered from their mothers by caesarean section on day 22 of gestation. Immediately thereafter, neonatal males were placed at an ambient temperature of either 18, 21, 24 or 30°C. With 2 h of exposure, the body temperature was in close correspondence with the ambient temperature. The PPTS was clearly abolished in the pups exposed for 2 h at either 18 or 21°C. The effect of temperature was reversible: by placing pups at either 18 or 21°C for 2 h after delivery, and then rewarming by placing them with a foster mother, the PPTS was delayed until 4 h after birth, i.e. 2 h after the beginning of rewarming. Thus, environmental cooling appears to retard the development of neural and/or endocrine systems mediating the PPTS. Aberrant maternal care which would produce substantial cooling of the male pups would be expected to affect the PPTS, which in turn might affect the sexuality of male progeny.


1986 ◽  
Vol 109 (2) ◽  
pp. R9-R11 ◽  
Author(s):  
W. v. Rechenberg ◽  
J. Sandow ◽  
P. Klatt

ABSTRACT Continuous administration of LH-releasing hormone (LHRH) agonists is an effective method of suppressing testosterone secretion in the male. The effect of the LH-releasing hormone (LHRH) agonist, buserelin, administered to bulls by constant infusion from osmotic minipumps was studied. In one experiment with four treated and one control bull, 109 pg buserelin/day were administered for 22 days. Immediately after implantation, serum testosterone concentrations rose from below 35 nmol/l to 35-105 nmol/l, and all four buserelin-infused bulls showed increased testosterone secretion during the treatment period. After removal of the minipumps, testosterone concentrations decreased to pretreatment levels. In a second experiment bulls were infused for 42 days (four treated and one control), and identical results were obtained. Testosterone secretion was stimulated (52-87 nmol/l serum) during the entire treatment period. These results demonstrate that conditions for stimulation of the pituitary-testicular axis may vary between species. Infusion of low doses of LHRH-agonists in bulls has an extended stimulatory effect without immediate desensitization of gonadotrophin release.


1995 ◽  
Vol 133 (3) ◽  
pp. 366-374 ◽  
Author(s):  
Robert F McGivern ◽  
Ralph HM Hermans ◽  
Robert J Handa ◽  
Lawrence D Longo

McGivern RF, Hermans RHM, Handa RJ, Longo LD. Plasma testosterone surge and luteinizing hormone beta (LH-β) following parturition: lack of association in the male rat. Eur J Endocrinol 1995; 133:366–74. ISSN 0804–4643 Studies examining the role of luteinizing hormone (LH) in the initiation of the postnatal surge of testosterone in the male rat have produced ambiguous results. We examined the pattern of postnatal LH secretion in the newborn male rat, coincident with plasma testosterone levels, using a specific monoclonal antibody for LH-β. In some males, we attempted to block LH secretion and the postnatal testosterone surge by injecting males with a gonadotropin-releasing hormone (GnRH) antagonist, an LH antibody or progesterone immediately after delivery by cesarean section on day 22. Following injection, animals were immediately sacrificed (time 0) or housed in a humidified incubator maintained at 30°C until sacrifice at 60, 120, 240, 360 or 480 min after delivery. Plasma from individual animals was measured subsequently for LH-β and testosterone by radioimmunoassay. Results revealed a postnatal surge of testosterone which peaked at 2 h after delivery in males from all treatment groups. This testosterone surge was not accompanied by a postnatal rise in plasma LH-β in any group. Administration of the GnRH antagonist or the ethanol vehicle produced a transient drop of approximately 25% in LH-β levels at 60 min but did not decrease the postnatal testosterone surge in the same animals. Additional studies in untreated males and females born by cesarean section or natural birth also failed to reveal a postnatal rise in plasma LH-β during the first 3 h after birth. Plasma levels in both sexes were significantly lower in animals delivered by cesarean section compared to natural birth. Overall, these results indicate that the postnatal surge of testosterone occurs without a corresponding surge of detectable LH-β in the male rat. Robert F McGivern, 6363 Alvarado Ct, Suite 200H. San Diego, CA 92120, USA


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