Integrated Concentrations of Luteinizing Hormone and Puberty PETER A. LEE, LESLIE P. PLOTNICK, RONALD E. STEELE, ROBERT G. THOMPSON, AND ROBERT M. BLIZZARD Department of Pediatrics, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 ABSTRACT. Integrated serum concentrations of luteinizing hormone have been compared among 30minute collections from 10 boys (6-18 years old) and 5 girls (5-11 years old). This study suggests that prepubertal as well as pubertal boys have

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ONCENTRATIONS of luteinizing hormone (LH) in early and mid-pubertal boys and girls have been reported to be increased significantly during sleep (1,2). Prepubertal children, late pubertal adolescents, and postpubertal individuals, in contrast, were reported to have similar concentrations of LH during waking and sleep (1,3). Our goal in the present report was to examine further the inter-relationship of the secretion of LH in the sleepwake cycle during the maturation of the hypothalamic-pituitary-gonada] axis. Materials and Methods

Ten boys and five girls, 5 to 18 years old, participated in the study. All were normal. Constant blood withdrawal using a Sigma motor pump with a non-thrombogenic catheter (4) was continued for 12 to 24 hours, with subperiods of 30 minutes each. Sleep was observed and recorded. Each individual's LH values were run in a single assay. Serum LH was measured, using a modification of a double-antibody radioimmunoassay described elsewhere (5), using LER 907 as assay Received April 14, 1975. Supported by Research Grants HD-01852, HD06284-02, and AM-00180-22 and by Traineeship Grant Ti-AM-5219-13 of the National Institutes of Health, United States Public Health Service. Patients were studied on the Pediatric Clinical Research Unit of the Johns Hopkins Hospital, supported by Grant 5-M01-RR-0052 from the General Research Centers Program of the Division of Research Resources, National Institutes of Health. Correspondence: Peter A. Lee, M.D., 3-110 Children's Medical Center, The Johns Hopkins Hospital, Baltimore, Maryland 21205.

greater mean integrated concentrations of LH during sleep than during waking. One of two pubertal girls had greater concentrations of LH during sleep, while three prepubertal girls did not. (J Clin Endocrinol Metab 43: 168, 1976)

standard. The intra-assay coefficient of variation for 10 replicate samples of a serum standard having a mean of 9.7 ng/200 fx\ was 4.3%, and the inter-assay coefficient of variation was 7.1%. Values of less than sensitivity in the LH assay, 1.6 ng/200 /Ltl sample volume, were assigned a value of 8.0 ng/ml for statistical evaluations. The stages of puberty are classified according to Tanner (6). The Student's t and paired t tests were used for statistical analysis. Informed consent was obtained for all studies.

Results

The integrated concentrations (IC) of LH are presented in Table 1 and in Figs. 1, 2, and 3. The calculated means are the averages of the determined luteinizing hormone concentrations in 30-minute specimens. The total number of awake specimens after the first 2 collections after the insertion of the withdrawal apparatus was used to obtain the calculated mean IC for the awake period. Early specimens were omitted to disregard the early data taken after the insertion of the pump, which might have been taken during a period of acclimatization. Four (nos. 2-5) of the five boys in stage I had a significantly greater mean integrated concentration of LH during sleep than during the awake period. The averages of the calculated means for the five boys in stage I were also higher (P < 0.05) during the sleep period (mean 38 ng/ml) than during the awake period (32 ng/ml). The three pubertal boys (nos. 6-8) and one postpubertal boy (no. 10) had significantly higher values during sleep than during the awake period. The mean IC LH during sleep (49

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INTEGRATED LH LEVELS AND PUBERTY

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TABLE 1. Comparison of mean integrated concentrations (int. cone.) ofLH during sleep and while awake Calculated integrated concentration (LER 907, ng/ml) Pubertal stage Number

Breast/ genital

Pubic hair

Age

Number of sleep samples

Int. cone, sleep

Number of awake samples

1 1 I I I

I I I I I

6 7/12 6 8/12 10 10/12 12 7/12 13 4/12

II II IV V V

11 11-1II IV V V

13 10/12 16 4/12 14 8/12 16 11/12 18 5/12

17 18 16 7 15

24.4 ± 27.3 ± 34.8 ± 44.3 ± 61.2 ±

1.0 0.8 0.9 1.2 2.9

27 19 29 37 31

23.6 ± 24.9 ± 25.1 ± 34.4 ± 54.1 ±

27 29 31 28 21

37.0 ± 26.5 ± 41.1 ± 36.8 ± 51.1 ±

18 16 12 15 10

44.9 ± 31.3 ± 57.5 ± 40.9 ± 69.6 ±

1.5 1.0 3.6 3.6 4.3

I I I 11 III

I I I 1 II

5 3/12 9 7/12 9 11/12 12 1/12 11 5/12

14 16 14 10 14

36.3 ± 0.8 33.1 ± 0.8 30.7 ± 0.9 78.5 ± 8.0 29.0 ±2.1

NS