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Biomedical subjects

L Dunkel

Publications and source records attributed to L Dunkel.

8 recordsLinked to original sources

Developmental changes in 24-hour profiles of luteinizing hormone and follicle-stimulating hormone from prepuberty to midstages of puberty in boys.

To establish the pubertal changes in gonadotropin secretion, 24-h secretory profiles of LH and FSH were studied in 10 healthy boys by ultrasensitive (sensitivity, 0.019 and 0.014 IU/L, respectively) time-resolved immunofluorometric assays 21 times. Five of the 10 boys were sampled on 2-6 occasions over a time interval of 0.95-6.4 yr. When sampled, 6 boys were prepubertal (testicular volume, less than 3 mL), 8 boys were early pubertal (testicular volume, 3-5 mL), and 7 boys were midpubertal (testicular volume, 10-25 mL). Plasma was taken every 20 min for 24 h. All boys had LH and FSH pulses. In prepuberty, the mean LH level was much lower than the mean FSH level, and neither showed significant diurnal variation. In early puberty, the mean LH level increased much more than that of FSH. For LH, the increase in mean levels was due to an increase in both pulse amplitude and frequency. During early and midpuberty, these changes were most marked at night, leading to the appearance of diurnal variation. For FSH, the mean levels increased progressively from prepuberty to midpuberty, with a slight increase in the mean pulse amplitude at the onset of puberty, whereas no change in pulse frequency was found. In contrast to LH, no diurnal variation was found for FSH at any of the pubertal stages. Thus, at the onset of puberty, gonadotropin secretion undergoes specific changes, which are different for LH and FSH, involving changes in pulse amplitudes and frequencies and development of diurnal variation for LH.

Adolescent

LH measurements by in vitro bioassay and a highly sensitive immunofluorometric assay improve the distinction between boys with constitutional delay of puberty and hypogonadotropic hypogonadism.

The basal and gonadotropin-releasing hormone (GnRH) stimulated levels of LH were measured in 21 boys with delayed puberty using conventional RIA, mouse interstitial cell in vitro bioassay (B-LH), and a highly sensitive immunofluorometric method (F-LH). On the basis of subsequent clinical follow-up, the subjects were diagnosed as idiopathic constitutional delay of puberty (CD, n = 13) or hypogonadotropic hypogonadism (HH, n = 8). The basal RIA LH levels were similar in the two diagnostic groups (HH, 2.92 +/- 0.76, CD 3.53 +/- 1.37 IU/L). In contrast, the mean basal B-LH was significantly lower in boys with HH than with CD (1.10 +/- 0.45 versus 2.91 +/- 1.23 IU/L; p less than 0.01). A similar finding was made by F-LH measurements which were clearly lower in the HH than the CD group (0.073 +/- 0.04 versus 1.71 +/- 0.97 IU/L, p less than 0.01). Also upon GnRH stimulation (3.5 micrograms/kg i.v.), the distinction between the CD and HH groups was better with the B-LH and F-LH measurements. The basal B/I ratio of the CD group (0.90 +/- 0.43) was more than that of the HH group (0.42 +/- 0.25, p less than 0.01) and this ratio increased significantly (more than 2-fold, p less than 0.01) during GnRH stimulation in the CD group, but not in the HH patients. Such differences were not found between the B/F ratios of the CD and HH groups. Measurements of basal and GnRH stimulated B- and F-LH levels clearly improved the distinction between CD and HH in comparison to the conventional RIA method, due to the low sensitivity and likely cross-reactions with some non-LH constituents of serum in the latter assay. This problem is, to a great extent, eliminated by better sensitivity and specificity of B-LH and F-LH measurements. For the same reasons, the difference in B/I ratios between the CD and HH samples, and the increased B/I ratio after GnRH stimulation in the CD group, were not observed in B/F ratios. In conclusion, the measurements of basal and GnRH-stimulated concentrations of serum B-LH and F-LH clearly improve the differential diagnostics between CD and HH. The discrepancies measured between the B/I and B/F ratios in these samples call for reevaluation of the bio/immuno ratios of circulating LH.

Adolescent

Pulsatile secretion of LH and FSH in prepubertal and early pubertal boys revealed by ultrasensitive time-resolved immunofluorometric assays.

Pulsatile secretion of LH and FSH was examined in 10 prepubertal (aged 4.5-12.9 y) and seven early pubertal (aged 12.8-14.5 y) boys with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. Plasma LH and FSH levels were measured every 15 or 20 min for 6 h during the day and night. The lowest mean LH level in a prepubertal boy was 0.02 IU/L and in eight other prepubertal boys mean LH levels were less than 0.4 IU/L. In early pubertal boys the mean LH levels ranged from 0.3 to 6.5 IU/L. The difference in mean FSH level between prepubertal (0.61 IU/L) and early pubertal boys (1.85 IU/L) was smaller than the difference in LH level. All boys had significant LH and FSH pulses. The LH interpulse interval was 135 +/- 86 min (mean +/- SD) and 76 +/- 65 min for the prepubertal and pubertal boys, respectively (p less than 0.01). For FSH, the respective values were 150 +/- 122 and 221 +/- 157 min (p = NS). The mean LH pulse amplitudes were 11-fold greater in the early pubertal boys than in the prepubertal boys, whereas the mean FSH pulse amplitudes were similar between the two groups. The present method shows that the mean LH levels in prepubertal boys are much lower, and the increase during puberty larger, than previously reported. The increase is apparently due to increased pulse frequency and amplitude. The increase in mean FSH level is smaller and evidently not caused by an increase in pulse frequency or pulse amplitude.

Adolescent

Gonadal control of pulsatile secretion of luteinizing hormone and follicle-stimulating hormone in prepubertal boys evaluated by ultrasensitive time-resolved immunofluorometric assays.

To elucidate the role of the testis in the control of LH and FSH secretion before puberty, we examined pulsatile LH and FSH secretion in six prepubertal boys with primary testicular failure (two boys with masculine pseudohermaphroditism, two boys with the Klinefelter's syndrome, and two boys with anorchia) and eight normal prepubertal boys. Plasma LH and FSH levels were measured every 15 min for 6 h during the day and night with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. In all six hypogonadal boys the mean FSH level was above the range of the normal prepubertal boys, whereas the LH level was elevated in only one boy. All boys had LH and FSH pulses. The FSH pulse interval in the anorchid boys was shorter than that in the normal boys, but this was not observed in the other hypogonadal boys. The LH pulse interval in the anorchid and other hypogonadal boys was the same as that in the normal boys. The FSH pulse amplitudes were higher in the anorchid and other hypogonadal boys than in the normal boys, but the LH pulse amplitudes were higher only in the anorchid boys. We conclude that in prepuberty the testes have little effect on LH secretion, but that they are involved in the regulation of FSH levels. In primary testicular failure, the elevation of FSH levels is associated with an increase in FSH pulse amplitude and, in the absence of testicular steroids, possibly also with an increase in FSH pulse frequency.

Age Factors

Testicular responsiveness to hCG during infancy measured by salivary testosterone.

To investigate the role of gonadotropins in postnatal testicular activation, testosterone responsiveness to human chorionic gonadotropin was studied in 11 male infants (aged 5-180 days). The boys were given a single im injection of 5000 IU/1.7m2 hCG, and serum and salivary testosterone responses were then measured for 7 days. The results were compared with the serum testosterone responses of 8 older prepubertal boys (aged 1.7-10.4 years) studied with the same protocol. The mean (+/- SEM) basal serum testosterone levels were 2.67 +/- 1.27 nmol/l in the infants and 0.09 +/- 0.02 nmol/l in the prepubertal boys (p less than 0.05). Both groups gave a significant response to hCG stimulation (p less than 0.001, ANOVA, one-way). The stimulated concentrations of serum testosterone were higher in the infants than in the prepubertal boys (p less than 0.001). The mean basal level of salivary testosterone was 30.5 +/- 7.0 and the mean maximal level was 97 +/- 10.3 pmol/l in the infants (p less than 0.001). No age-related changes were observed in either basal or hCG-stimulated levels. In infants the mean (+/- SEM) maximal hCG-stimulated increase was 25 +/- 10-fold in serum and 8 +/- 4-fold in saliva (p = 0.13). A clear stimulatory effect of hCG on testicular testosterone production was found, suggesting that the postnatal increase in serum testosterone concentration in male infants is gonadotropin-mediated. Salivary testosterone concentrations can be increased by hCG, indicating that measurements of salivary testosterone may provide an optional, non-invasive method for assessing gonadal function in children.

Aging

Growth after treatment of solid tumours in childhood.

We examined 90 survivors of childhood solid tumours diagnosed in our hospital between 1960 and 1976. Their ages at the time of this study ranged from 12.2 to 41.5 years. Adult standing height was usually normal. However, final standing height was less than expected in the females, and sitting height was below the normal mean in the males. The males who had received both chemotherapy and radiation therapy to the spine had a greater decrement in sitting height, but we did not find any association between radiation therapy to the spine without chemotherapy and subsequent total growth of the spine as measured by sitting height. We conclude that these children generally do not experience any major growth disturbances.

Adolescent

Hypergonadotropic hypogonadism and sperm abnormalities in men born with benign sacrococcygeal teratoma.

To elucidate the hypothetical role of a primary germ cell defect in the development of a germ cell tumor, with subsequent testicular dysfunction, the authors studied a series of men who had surgery performed for a benign sacrococcygeal teratoma when newborns. The mean levels of serum testosterone and gonadotropins did not differ from the control patients. However, gonadotropin-releasing hormone stimulation caused exaggerated responses of serum luteinizing hormone and follicle-stimulating hormone. Testicular size was small in three of eight patients. Semen analysis showed abnormal semen quality in five of eight patients. Only one patient had no evidence of testicular dysfunction. The results indicate that men born with benign sacrococcygeal teratoma may have Leydig cell dysfunction, abnormal spermatogenesis, or both. It was speculated that the associated abnormalities may have a common etiology: for instance, they might be due to a congenital germ cell defect.

Adult