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Biomedical subjects

L Dunkel

Publications and source records attributed to L Dunkel.

At least 55 records · Page 3Linked to original sources
PubMed1996

Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty.

Determinations of serum gonadotropin concentrations by ultra-sensitive methods have improved the diagnosis of pubertal disorders. The onset of puberty can be estimated by measuring serum gonadotropin pulsation, but as this requires serial nocturnal blood sampling, it is not a routine investigation. Gonadotropin measurements in first morning voided (FMV) urine samples could reflect the integrated nocturnal gonadotropin secretion and predict pubertal development earlier than daytime serum measurements. We studied the value of urinary LH (U-LH) measurements in FMV urine with reference to serum LH (S-LH) levels using an ultrasensitive time-resolved immunofluorometric assay in samples from 297 children and adolescents (145 boys and 152 girls, aged 5-15 yr) with known pubertal stages (Tanner 1-5). Stage 1 subjects (prepubertal) were divided into 5 age groups to assess whether there is an increase in LH before clinical signs of puberty can be detected. The correlation between FMV urine and S-LH values was good (r = 0.64; P < 0.0001). The 2 oldest groups of prepubertal subjects (11 and 12 yr) had significantly higher (P < 0.001) U-LH concentrations than the 3 younger groups. This difference was less marked for S-LH. A significant increase in FMV U-LH concentration occurs before the first clinical signs of puberty in a sex-independent fashion. Our data indicate that FMV U-LH measurement is a clinically relevant, noninvasive method for the evaluation of pubertal development, and it may be helpful in the investigation of pubertal disorders.

Aging↗
PubMed1996

The role of luteinizing hormone-beta gene polymorphism in the onset and progression of puberty in healthy boys.

An immunologically anomalous LH with two point mutations in its beta-subunit gene (Trp8Arg and Ile15Thr) has recently been described. This polymorphism is common in Finland; 28% of the population are homo- or heterozygous for the variant allele. To assess the effect of the LH variant on LH action, we correlated its presence in a group of 49 healthy boys with the onset and progression of puberty. This group was followed-up longitudinally from a mean age of 11.7 +/- 0.1 yr for 3 yr at 3-month intervals. In addition, we studied the prevalence of the variant LH in boys with constitutional pubertal delay (testicular volume < or = 4 mL after 13.5 yr of age). The LH beta gene status of each subject in this study was judged from a single venous blood sample using two immunofluorometric LH assays with different combinations of monoclonal antibodies: one detecting both the variant and wild-type LH, and the other detecting only wild-type hormone. Of the boys with pubertal onset at a normal age, 36 (74%) were homozygous for the wild-type LH beta allele, 12 (24%) were heterozygous, and 1 (2%) was homozygous for the variant LH beta allele. Clear differences in pubertal parameters were found between the boys with normal and mutated (homo- or heterozygous) LH genotypes. During the follow-up, the boys with the mutated genotype had smaller testicular volumes (P < 0.03), were shorter (P < 0.02), had slower growth rates (P < 0.04), and had lower serum insulin-like growth factor I-binding protein-3 levels (P < 0.03) than the boys with the normal LH genotype. In the boys with delayed onset of puberty, the frequency of the variant LH beta allele did not differ from that in the reference population, indicating that the variant LH is not associated with conditions due to disturbed control of the reactivation of GnRH secretion. We conclude that during the progression of puberty, the variant LH may be less active in stimulating testicular growth than wild-type LH. Thus, the gene may affect tempo, contributing to the wide normal variation in pubertal progression in healthy boys. Our results also suggest that the variant LH not only affects the course of puberty, but is already involved in the regulation of the GH-insulin-like growth factor I axis during childhood.

Adolescent↗
PubMed1995

Expression of luteinizing hormone and chorionic gonadotropin receptor messenger ribonucleic acid in human corpora lutea during menstrual cycle and pregnancy.

In the present study, we examined the expression of LH and CG receptor messenger RNA (mRNA) in human corpora lutea (CL) during the menstrual cycle and pregnancy. Poly(A)-enriched RNA was extracted from CL and analyzed by Northern and slot blots, using a radiolabeled complementary RNA probe derived from the human LH receptor complementary DNA. Northern blot analysis indicated the presence of multiple LH receptor mRNA transcripts with molecular sizes of 8.0, 7.0 and 4.5 kilobases in human CL during the menstrual cycle. The predominant transcript was 4.5 kilobases in size. However, no hybridization signals were observed in nongonadal tissues (heart, liver, and kidney). Densitometric analyses revealed that the levels of LH receptor mRNA increased from early luteal phase to midluteal phase and subsequently decreased during late luteal phase. After the onset of menstruation, the LH receptor mRNA level was undetectable in the regressing CL. Moreover, radioligand receptor assay (RRA) showed a close parallelism between LH receptor mRNA levels and LH receptor content in CL throughout the menstrual cycle. LH receptor mRNA expression was also found in CL during early pregnancy. The level of LH receptor mRNA was relatively high in early pregnancy CL, whereas LH receptor content was low. Using in situ hybridization, LH receptor mRNAs were uniformly expressed in both large and small luteal cells during early and midluteal phase and early pregnancy, but not in regressing CL. In conclusion, these data demonstrate that the regulation of LH receptor content in human CL during luteal phase is associated with similar changes in the receptor message levels, suggesting the physiological roles for LH receptor mRNA during the menstrual cycle in the human. In addition, the expression of LH receptor mRNA was demonstrated in human CL during early pregnancy.

Adult↗
PubMed1995

Age-related course of urinary gonadotropins in children.

Serum levels of LH and FSH are very low from about 2 yr of age to the onset of puberty, which is heralded by a very sharp increase in LH levels. We studied age-related changes in urinary gonadotropins in a total of 184 boys and girls of various ages. Urinary FSH and LH were measured by ultrasensitive time-resolved immunofluorometric assays. The detection limit was 0.015 IU/L for LH and 0.018 IU/L for FSH. We observed that after an initial drop following the first months of life, urinary LH levels stayed below 0.5 IU/L until age 9 yr in girls and below 1.0 IU/L until age 11 yr in boys, whereas mean urinary FSH levels remained below 3.0 IU/L until age 10 yr in girls and 12 yr in boys. During puberty, mean urinary FSH and LH concentrations increased to about 5 IU/L in boys and 10 IU/L in girls. This corresponds to a 5-fold increase in FSH in both sexes and a 50- to 100-fold increase in LH in boys and girls, respectively. These dynamic changes agree with previous reports regarding serum levels, suggesting that noninvasive urinary gonadotropin measurements can be a viable alternative to serum determinations in the evaluation of gonadotropin secretion during childhood and adolescence.

Adolescent↗
PubMed1994

Follicle-stimulating hormone receptor expression in the rat ovary: increases during prepubertal development and regulation by the opposing actions of transforming growth factors beta and alpha.

Pituitary gonadotropin FSH acts exclusively on ovarian granulosa cells by binding to specific plasma membrane receptors. Transforming growth factors alpha and beta (TGF alpha and TGF beta), produced locally within the ovary, have been shown to regulate diverse follicle functions, although their potential role in the regulation of FSH receptors has not been assessed. Our first objective was to demonstrate developmental changes in the expression of FSH receptor gene and protein; we then analyzed the regulation of FSH receptor expression by TGF beta s and TGF alpha in cultured granulosa cells. Analysis of steady-state FSH receptor mRNA and protein levels in neonatal and prepubertal ovaries revealed the existence of two predominant FSH receptor mRNA transcripts, 7.0 and 2.5 kb in size, showing a dramatic increase between Day 15 and Day 18 of age followed by a plateau up to 27 days of age. A close parallelism in the developmental changes in FSH receptor mRNA levels and FSH receptor content was observed. Cultured granulosa cells obtained from estrogen-treated immature rats exhibited FSH receptor transcripts similar in size to those seen in whole ovaries. Treatment of granulosa cells for 48 h with TGF beta 1 increased the levels of FSH receptor mRNA for both the 7.0- and 2.5-kb transcripts in a dose-dependent manner (ED50, 1.5 ng/ml), with a maximal 4.0 +/- 0.8-fold increase over control levels observed in response to 10 ng/ml TGF beta 1. Also, TGF beta 2 was as potent as TGF beta 1 in increasing FSH receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reduced inhibin and elevated gonadotropin levels in early pubertal boys with testicular defects.

In the prepubertal quiescent period, the control of gonadotropin secretion is assumed to be mediated by neuroendocrine inhibitory mechanisms, whereas little or no effect is thought to be mediated by the gonad. However, in pubertal-aged children with primary gonadal failure, gonadotropins increase to supranormal levels, suggesting that gonadal factors become more important in the control of gonadotropin secretion at that age. These gonadal factors have been poorly characterized so far. To clarify the relationship of inhibin and testosterone to the control of gonadotropin secretion during sexual maturation, we examined serum inhibin, testosterone, LH, and FSH concentrations in 10 boys with testicular defects and in nine healthy boys, in prepuberty and in early puberty. Serum was obtained at 15-min intervals for at least 6 h during the night. Prepubertal-aged boys with testicular defects had only slightly higher FSH levels than healthy boys, and their LH and inhibin levels were no different. In contrast, pubertal-aged boys with testicular defects had higher LH and FSH levels and lower inhibin levels than healthy boys. In prepubertal-aged boys, no correlation was found between individual mean inhibin level and mean FSH or LH level. In contrast, in pubertal-aged boys, an inverse nonlinear relationship between mean inhibin level and mean FSH and LH level was seen. The inverse value for inhibin correlated with FSH (r = 0.74, p < 0.01) and with LH (r = 0.81, p < 0.01). In conclusion, our results suggest that inhibin is a factor involved in the control of gonadotropin secretion in boys, at least in the pubertal period.

Adolescent↗
PubMed1993

Deglycosylated human chorionic gonadotropin (hCG) antagonizes hCG stimulation of 3',5'-cyclic adenosine monophosphate accumulation through a noncompetitive interaction with recombinant human luteinizing hormone receptors.

In the rat, the antagonistic properties of deglycosylated (dg) gonadotropins in vitro are characterized by high affinity receptor binding but impaired ability to stimulate cAMP accumulation. In human, the functional role of N-linked sugars in human CG (hCG) action is unclear because of the unavailability of totally deglycosylated hCG and because of the difficulty involved in obtaining human gonadal tissues. We have recently prepared completely deglycosylated hCG using site-directed mutagenesis and expressed functional human LH (hLH) receptors using cloned complementary DNA. Since hLH receptor shows distinct ligand specificity from that of rat LH receptor, we examined binding kinetics and signal transduction of recombinant dg-hCG using recombinant hLH receptors. In embryonic human kidney cells (293) transfected with hLH receptor complementary DNA, 125I-hCG binding to its receptor was studied in the presence of varying amounts of unlabeled dg-hCG or wild type (WT)-hCG. Lineweaver-Burk analysis of the binding kinetics showed that the displacement of 125I-hCG by dg-hCG was noncompetitive whereas that seen for WT-hCG was competitive. The noncompetitive nature of dg-hCG binding was further confirmed using rat LH receptors present in testis membrane preparations. After preincubation of LH receptor-expressing 293 cells with WT-hCG, inclusion of 125I-hCG competitively displaced WT-hCG. In contrast, preincubation with dg-hCG prevented subsequent 125I-hCG binding to human LH receptor for at least 46 h. WT-hCG caused a dose-dependent increase in cAMP accumulation in the 293 cells with an ED50 of 10 ng/ml. However, dg-hCG was ineffective in inducing cAMP production with a maximal effect of only 12% of that stimulated by WT-hCG. In the presence of increasing doses of dg-hCG, stimulation of cAMP by WT-hCG was antagonized in a dose-dependent manner. In contrast, forskolin stimulation of cAMP was not antagonized by dg-hCG, indicating receptor-mediation of dg-hCG action. Similar to binding studies, preincubation with dg-hCG also dose-dependently blocked the subsequent stimulatory effect of WT-hCG on cAMP production. Thus, the noncompetitive binding of dg-hCG to hLH receptors and its antagonism of hCG stimulation of cAMP accumulation suggest that dg-hCG is an irreversible receptor blocker with unique antagonistic properties.

Animals↗
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↗