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Biomedical subjects

L Dunkel

Publications and source records attributed to L Dunkel.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants.

We studied the hormonal background of the fluid derangements and arterial hypertension associated with adrenocorticotrophic hormone (ACTH) treatment for infantile spasms in ten infants aged 5-22 months. They received a 6 week course of (carboxymethyl-cellulose-)ACTH: 80 IU at 0800 hours daily in weeks 1-3, then tapering, and termination at the end of week 6. The infants showed large, variable increases in 24 h urine cortisol during treatment. The mean plasma cortisol concentration (24 h after ACTH injection) was not significantly increased, but was correlated with the relative dose of ACTH. The mean plasma aldosterone concentration decreased. No significant change occurred in plasma renin activity (PRA), or in the concentrations of renin substrate (RS) or arginine vasopressin (AVP). Seven infants developed arterial hypertension, which was severe in three. This severe hypertension was associated with the highest relative ACTH doses and the highest plasma RS and cortisol concentrations. In the group as a whole, systolic blood pressure correlated with plasma RS and cortisol concentrations, but not with the other parameters. At the end of treatment urine and plasma cortisol dropped below the pretreatment levels and stayed low for greater than 2 weeks. There was a sharp peak in PRA and plasma aldosterone concentration, and a decrease in plasma RS. Plasma AVP levels dropped markedly. The mean body weight increased sharply and urine flow decreased. Mean plasma electrolyte levels remained unaltered. The danger at termination of ACTH treatment appears to be associated with a sudden transition from hypercortisolism to hypocortisolism, activation of the renin-angiotensin-aldosterone axis, and suppression of AVP secretion.

Adrenocorticotropic Hormone↗
PubMed1988

Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes.

Sex steroids influence serum high density cholesterol (HDL) concentrations through their effects on postheparin plasma hepatic lipase activity. This enzyme is remarkably sex steroid sensitive; its activity is increased by treatment with androgens and androgenic progestins but decreased by estrogens. Hepatic lipase also is regulated by endogenous estradiol, but less is known about its regulation by endogenous androgens. We measured serum lipoproteins and postheparin plasma hepatic lipase and lipoprotein lipase activities in relation to sex steroids in 13 boys in whom testicular sex steroid production was stimulated by 4 injections of hCG given at 3-day intervals. Serum testosterone, but not estradiol, concentrations increased in 8 boys (group I, prepubertal and early pubertal boys), whereas in 5 boys both testosterone and estrogen concentrations increased concomitantly (group II, pubertal boys). Postheparin plasma hepatic lipase activity increased by 34% (P less than 0.001) in group I, but did not change in group II. Serum HDL cholesterol concentrations did not change during hCG stimulation. However, postheparin plasma hepatic lipase activity correlated inversely with serum HDL (r = -0.34; P less than 0.05) and HDL2 cholesterol levels (r = -0.51; P less than 0.001), and the changes in HDL2 levels and hepatic lipase activity were inversely related (r = -0.63; P less than 0.05). Postheparin plasma lipoprotein lipase activity decreased during hCG stimulation. Its activity was positively related to HDL (r = 0.47; P less than 0.05) and HDL2 cholesterol levels (r = 0.54; P less than 0.001). These results suggest that endogenous androgens and estrogens are involved in the regulation of postheparin plasma lipase activities and serum HDL cholesterol concentrations.

Adolescent↗
PubMed1987

Impaired prolactin responsiveness to a dopamine antagonist in long-term survivors of acute lymphoblastic leukaemia.

Cranial irradiation is known to affect the neuroendocrine control of GH secretion. The aim of the present study was to clarify the effect of leukaemia treatment on neuroendocrine control of PRL secretion in long-term survivors of acute lymphoblastic leukaemia (ALL). Pituitary LH, FSH and PRL responses to GnRH and to the dopamine receptor antagonist metoclopramide were evaluated in 18 boys 1.6-9 years after discontinuation of medication for ALL. All the boys had been subjected to prophylactic cranial irradiation and 8 to testicular irradiation. Eight of the boys had supranormal gonadotropin levels either basally or after GnRH. All had normal basal PRL levels, but in 14 of the 18 boys the metoclopramide-releasable PRL levels were subnormal. The decreased PRL responses cannot be explained by the hypergonadotropism, since exaggerated rather than decreased responses are frequently found in patients with primary gonadal failure. We conclude that abnormal regulation of PRL secretion is a frequent consequence of treatment of ALL, probably being due to decreased pituitary lactotrop mass.

Antineoplastic Agents↗
PubMed1986

Adrenocortical hyporesponsiveness after treatment with ACTH of infantile spasms.

The hypothalamic-pituitary-adrenocortical axis was studied in 10 infants before and during a six week period of treatment with adrenocorticotrophic hormone (ACTH) and three days and one and two weeks after its stopping. During the treatment 24 hour urinary cortisol excretion increased 20 to 350-fold (mean 100) above the basal value. Mean morning serum cortisol concentration, measured 24 hours after the preceding ACTH dose, did not increase. After the treatment mean urinary cortisol excretion was subnormal and mean morning serum cortisol concentration was below the pretreatment value. The mean serum cortisol response to a vasopressin test was reduced and shortened throughout the post-treatment observation period. The mean serum cortisol response to an intravenous ACTH test was not significantly different from the pretreatment response three days after treatment but was clearly reduced thereafter. At one and two weeks after treatment the basal concentrations of serum cortisol of one third of the patients and the post-ACTH concentrations of two thirds were subnormal. We conclude that in infants treatment with ACTH may cause adrenocortical hyporesponsiveness.

Adrenocorticotropic Hormone↗
PubMed1986

Transient increase in postnatal testicular activity is not revealed by longitudinal measurements of salivary testosterone.

Testicular steroidogenic activity in 22 boys was monitored longitudinally over the first 6 months of life using salivary T measurements. Samples were collected biweekly. The highest T levels, 130 +/- 12 pmol/liter (mean +/- SE, n = 22), were observed on days 2-10. The values then gradually declined to a mean of about 30 pmol/liter after month 4. No secondary peak in salivary T appeared, in contrast to the 1-3 month peak in serum T previously reported. The overall levels of T, reflected by the areas under the T concentration curves over the whole period, varied by a factor of three among the subjects studied. It is concluded that postnatal testicular activity may have its most marked physiologic effects immediately after birth rather than at the time of the 1-3-month peak of serum T. Furthermore, the overall exposure to androgen is individually greatly variable.

Age Factors↗
PubMed1986

Metoclopramide test in the diagnosis of isolated hypogonadotrophic hypogonadism.

The responses of serum prolactin (Prl) to metoclopramide and LH and FSH to GnRH were studied simultaneously in 9 boys with hypogonadotrophic hypogonadism (HH), 7 boys with constitutional delay of puberty (D) and 15 controls. Metoclopramide increased the Prl levels in all groups. The boys with HH had lower Prl responses than the controls, whereas the boys with D had similar responses to the controls. Of the 9 boys with HH, 8 had subnormal Prl responses, 3 subnormal LH and none subnormal FSH. A metoclopramide test is clearly more sensitive than a GnRH test in differentiating HH and D and appears to make the differentiation between these two conditions clearer.

Adolescent↗
PubMed1985

GnRH and HCG tests are both necessary in differential diagnosis of male delayed puberty.

The discriminative power of the gonadotropin releasing hormone test and the human chorionic gonadotropin (HCG) test in the diagnosis of gonadotropin deficiency was studied in 73 boys referred because of delayed pubertal development or suspicion of gonadotropin deficiency. Hypogonadotropic hypogonadism was confirmed by clinical follow-up in 21 of the boys and excluded in the others because of normal pubertal development. Those latter boys served as a reference group. The post-HCG serum testosterone level was subnormal in hypogonadotropic hypogonadism on 12 of 19 occasions (in the reference group on two of 46 occasions) and the post-gonadotropin releasing hormone serum luteinizing hormone level was subnormal on fourteen of 22 occasions (zero of 65). Four of the seven boys with hypogonadotropic hypogonadism who had normal post-HCG testosterone levels had subnormal peak luteinizing hormone levels. Of the remaining three boys, two had low basal testosterone levels. Combining the two tests therefore improved the diagnostic accuracy.

Adolescent↗
PubMed1985

Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys.

The discriminatory power of a gonadotropin-releasing hormone test and a human chorionic gonadotropin test in diagnosing gonadotropin deficiency was studied in 23 prepubertal boys with hypogonadotropic hypogonadism (HH). The boys were originally referred because of genital hypoplasia, delayed sexual maturation, or suspicion of HH. The diagnosis of HH was established clinically, in most cases after follow-up of several years. The results were compared with those of a reference group consisting of 44 prepubertal boys with incomplete testicular descent. Post-hCG serum testosterone level was the most sensitive discriminating variable, and was subnormal in 11 of 12 boys with HH (in one of 16 in the reference group). Post-GnRH serum LH concentration was the second most sensitive, and was subnormal in 15 of 23 boys with HH (two of the reference group). Our data indicate that post-hCG testosterone levels are of greater value than post-GnRH gonadotropin levels in the diagnosis of HH in prepubertal boys.

Adolescent↗