naloxone and Puberty--Precocious

The aim of the present study was to evaluate the activity of opiate receptors involved in the control of LH secretion during pubertal development, as determined by the LH response to naloxone. Normal children (n = 28) of both sexes, subdivided according to breast (girls) or testicular (boys) development, and patients with idiopathic precocious puberty (n = 7), delayed puberty (n = 8), or hypergonadotropic hypogonadism (n = 4) were studied. Plasma LH levels were measured after the administration of naloxone (NLX; 0.08 mg/kg BW, iv), GnRH (50 micrograms, iv) or placebo. In healthy subjects, NLX significantly increased plasma LH levels only in girls and boys at the most advanced stage of gonadal maturation. NLX was ineffective in prepubertal and early pubertal children, and it did not significantly alter LH levels in children with delayed puberty or hypogonadism or in most of the children with precocious puberty. GnRH injection consistently increased plasma LH levels in healthy subjects as well as in the children with pubertal disturbances. These results indicate that the LH response to NLX occurs only at the most advanced stages of pubertal maturation when normal or precocious and is absent in early puberty or in children with pubertal disturbances. Furthermore, the results suggest that opioid regulation of LH secretion in humans changes during puberty, reaching an adult-like functional state with maturation of the hypothalamus-pituitary-gonadal axis.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Naloxone; Puberty, Delayed; Puberty, Precocious

We tested the hypothesis that the improved sensitivity of immunofluorometric (IFMA) assays will lead to an increase in the number of detectable LH pulses compared to RIA in early pubertal boys, in whom LH secretion is low. To test this hypothesis we determined plasma LH concentrations in six pubertal boys (bone age, 12-16 yr) by IFMA and compared the results to RIA data reported previously. Each boy was given an infusion of saline, followed 1 week later by an infusion of testosterone (T; 960 nmol/h) for 33 h starting at 1000 h. Starting at 1200 h, blood was obtained every 15 min for LH determinations (RIA and IFMA) and every 30 min for T measurements. At the end of both studies, responses to GnRH (250 ng/kg) were assessed. The assay sensitivities for LH by RIA and IFMA (Delfia hLH Spec Pharmacia Diagnostics ENI, Columbia, MA) were 1.0 and 0.05 IU/L, respectively. LH pulses were identified by three independent pulse detection programs: Detect, Cluster, and Kushler-Brown. The correlation for LH values as measured by RIA and IFMA was highly significant (r = 0.81). There was a poor correlation between LH values determined by IFMA and RIA when LH values within 4 times the SD of each assay sensitivity were compared (r = 0.08; P = NS). T infusion suppressed LH pulse frequency by 40% and 66%, as determined by RIA and IFMA, respectively (P = NS). Using the Detect program, during the complete study in all 6 boys, 117 pulses of LH were identified by RIA and 93 by IFMA (79% ratio of detection IFMA/RIA). During saline infusion there were 73 vs. 69 LH pulses (94%), while during T infusion there were 24 vs. 44 LH pulses (55%), as detected by IFMA vs. RIA, respectively. Administration of naloxone did not accelerate LH pulse frequency during T infusion, as determined by either method. Changes in pituitary responses to exogenous GnRH also showed similar trends of augmentation by T infusion by both methods. We conclude that the use of IFMA does not lead to the anticipated increase in the detectability of LH pulsatility. Actually, fewer LH pulses were identified by IFMA in this group of boys. We speculate that this is due to the increased specificity of the IFMA assay. More significant was the finding that the physiological interpretation of the effects of T and naloxone on LH pulse frequency and responses to GnRH did not change whether LH was measured by RIA or IFMA.

Topics: Adolescent; Adult; Fluoroimmunoassay; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Naloxone; Puberty, Precocious; Pulsatile Flow; Radioimmunoassay; Sensitivity and Specificity

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal healthy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulatory and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.

Topics: Adolescent; Adult; Child; Female; Humans; Hypogonadism; Luteinizing Hormone; Male; Menstrual Cycle; Naloxone; Polycystic Ovary Syndrome; Puberty; Puberty, Delayed; Puberty, Precocious