Synchronization of Augmented Luteinizing Hormone Secretion with Sleep during Puberty

Boyar, Robert M.; Finkelstein, Jordan W.; Roffwarg, Howard P.; Kapen, Sheldon; Weitzman, Elliot D.; Hellman, Louis M.

doi:10.1056/nejm197209212871203

Cited by 492 publications

(166 citation statements)

References 11 publications

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“…The increase in serum testosterone in boys with testicular volumes of 1 ml to 2 ml is probably due to the start of adrenarche, as it increases in parallel with DHEAS. Reactivation of the gonads during puberty is evidenced by a change in diurnal rhythm, with an earlier nocturnal rise in testosterone secretion, consistent with rapid eye moment and sleep-induced secretion of gonadotropins (31). In recent years, direct RIAs for measurements of free testosterone have become available (32,33).…”

Section: Discussionmentioning

confidence: 99%

Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty

Ankarberg‐Lindgren

Norjavaara

2004

European Journal of Endocrinology

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Objective: To establish levels for comparison for 24-h total and free serum testosterone in prepubertal boys and throughout pubertal development. Design: The study subjects were 55 healthy boys, aged 5.0-18.6 years, who underwent serial sampling one or more times during their pubertal development. Methods: Testicular volumes were determined by orchidometer. Serum testosterone was measured by a modified RIA (detection limit, 0.03 nmol/l). Free testosterone was calculated (calc-FT) using a formula derived from the law of mass action. Results: Significant increases in testosterone and calc-FT concentrations in boys were found between testis volumes of 1 ml to 2 ml, 2 ml to 3 ml, 6 ml to 8 ml, and 10 ml to 15 ml. No differences were found between testis volumes of 3, 4, 5 and 6 ml neither were there differences between 8 and 10 ml, or between 15, 20 and 25 ml. Boys who had reached their final height had higher calc-FT values than boys who had the same pubertal development but had not reached their final height. Based on the results, puberty was classified into six stages: pre1 (testis, 1 ml), pre2 (testis, 2 ml), early (testis, 3 -6 ml), mid (testis, 8-12 ml), late1 (testis,15 -25 ml, not reached final height) and late2 (testis, 15 -25 ml, reached final height). Serum testosterone was secreted with a diurnal variation in prepuberty and during puberty. The increase of testosterone in the morning hours started earlier in pubertal than in pre-pubertal boys. The most pronounced diurnal rhythm was found in early and in mid puberty. Conclusion: Using a sensitive method, and a pubertal reclassification, we have established levels for comparison of testosterone and calc-FT in prepubertal and pubertal boys. The existence of data for comparison forms the basis for future studies on pubertal disorders.

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Section: Discussionmentioning

confidence: 99%

Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty

Ankarberg‐Lindgren

Norjavaara

2004

European Journal of Endocrinology

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“…12 All samples were collected between 09.00 and 10.00 h to minimise diurnal variation. 13 In the course of management, patients with low or low-normal testosterone levels were offered testosterone replacement therapy (TRT) and their clinical and biochemical responses were recorded. The study was approved ethically by the committee of the University College London Hospitals NHS Trust.…”

Section: Methodsmentioning

confidence: 99%

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies

Chatterjee

Andrews

Mcgarrigle

et al. 2000

Bone Marrow Transplant

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Summary:We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 ؎ 2.4 ml vs 20 ؎ 2.0 ml; P Ͻ 0.001), elevated gonadotrophins (FSH = 18.54 ؎ 7.61 vs 5 IU/l (P Ͻ 0.001); LH = 8.02 ؎ 2.89 vs 3.9 IU/l (P Ͻ 0.001)) and low normal mean testosterone levels (16.4 nmol/l ؎ 9.1 vs 22.4 nmol/l (P Ͻ 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED. Keywords: high-dose chemotherapy; bone marrow transplantation; cavernosal arteriogenic insufficiency; erectile dysfunctionThe long-term survival of recipients of high-dose chemotherapy (HDC) with or without total body irradiation (TBI) for haematological and non-haematological malignancies has risen dramatically in the last decade, yet little is known about the quality of life of the long-term survivors. Gonadal dysfunction is the most common long-term side-effect in the high-dose therapy and bone marrow transplantation (BMT) setting and is associated with significant morbidity. We 1 and others have shown germ cell damage 2 as well as Leydig cell insufficiency (low basal and HCG-stimulated testosterone levels) in such patients. 3 We have also shown that high-dose chemo-radiotherapy causes acute functional castration in patients with haematological malignancies within 72 h of TBI and there is a 50% loss of testicular volume. Subsequently patients may present with premature andropause. 1 Sexual dysfunction is a commonly recognised presentation in patients with ...

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“…During fetal development human chorionic gonadotropin, which binds to LH receptors, is present at concentrations 5000 times higher than during young adulthood. With the onset of menopause/andropause, LH concentrations increase to consistently higher levels (73,74). Interestingly, the increase in LH is higher and occurs earlier in women, who are more susceptible to AD than men.…”

Section: Contribution Of Sex Steroids and Gonadotropins To Amyloidosis-mentioning

confidence: 99%

Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition

Bowen

Verdile

Liu

et al. 2004

Journal of Biological Chemistry

165

132

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Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-␤ (A␤) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether A␤ generation was due to the loss of serum 17␤-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain A␤1-42 and A␤1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-␤ precursor protein (A␤PP) expression but did alter A␤PP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of A␤, decreased ␣A␤PP secretion, and increased A␤PP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote A␤ secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD.Alzheimer's disease (AD) 1 is a neurodegenerative disorder of the elderly that leads to progressive memory loss, impairments in behavior, language, visuo-spatial skills, and ultimately death. The one or more underlying biochemical mechanisms leading to AD are unknown. Genetic studies have shown that mutations in A␤PP and the presenilin genes lead to early onset (Յ65 years) AD, which accounts for ϳ5% of all AD cases. The vast majority of these mutations promote the overproduction and deposition of amyloid-␤ (A␤) (1-7), the major component of the extracellular amyloid plaques, in the hippocampus and frontal cortex (8,9). Amyloid deposition also is a hallmark of the late-onset or "sporadic" form of AD, which accounts for ϳ95% of AD cases. The primary factors responsible for A␤ deposition and disease progression in late onset AD remain to be elucidated.Aging, the strongest risk factor for late-onset AD, is associated with major changes in serum concentrations of all hormones that comprise the hypothalamic-pituitary-gonadal (HPG) axis, including declines in the serum concentrations of the sex steroids, 17␤-estradiol and testosterone. Such changes have been correlated with the prevalence of the disease (e.g. Refs. 10 -14), and it has been shown that there is a decreased i...

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Synchronization of Augmented Luteinizing Hormone Secretion with Sleep during Puberty

Cited by 492 publications

References 11 publications

Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty

Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies

Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition

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