Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis

Caron, Philippe; Bennet, A.; Plantavid, Monique; Jp, Louvet

doi:10.1530/eje.0.1310156

Cited by 11 publications

(5 citation statements)

References 13 publications

(16 reference statements)

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“…22.16). These symptoms are similar to those observed in patients with chemical castration using estrogens to treat prostatic carcinoma, or those seen in cases with excessive estrogen levels due to tumors of Sertoli or Leydig cells [108].…”

Section: Adrenocortical Tumorssupporting

confidence: 70%

Perspectives in Pediatric Pathology, Chapter 22. Testicular Involvement in Systemic Diseases

et al. 2016

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Normal testicular physiology requires appropriate function of endocrine glands and other tissues. Testicular lesions have been described in disorders involving the hypothalamus-hypophysis, thyroid glands, adrenal glands, pancreas, liver, kidney, and gastrointestinal tract. Testicular abnormalities can also associate with chronic anemia, obesity, and neoplasia. Although many of the disorders that affect the above-mentioned glands and tissues are congenital, acquired lesions may result in hypogonadism in children and adolescents.

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Section: Adrenocortical Tumorssupporting

confidence: 70%

Perspectives in Pediatric Pathology, Chapter 22. Testicular Involvement in Systemic Diseases

et al. 2016

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“…Computer algorithms detected 3 LH pulses and 4 FAS pulses of small amplitude (0.3 ± 0.1 IU/L and 0.2 ± 0.2 IU/L, respectively). Although the number of pulses was normal (19), the secretory patterns were erratic, and only 1 LH pulse and FAS pulse were coincident (20,21). Administration of the GnRH analogue agonist triptorelin/decapeptyl (Ipsen Biotech, Paris, France) induced a dramatic and progressive increase in FSH, LH, FAS, and testosterone concentra- (Figure 2, a and b).…”

Section: Resultsmentioning

confidence: 99%

A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism

Tabarin¹,

Achermann²,

Récan³

et al. 2000

J. Clin. Invest.

176

131

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IntroductionThe DAX1 gene encodes an orphan member of the nuclear receptor superfamily that lacks the typical zinc finger DNA-binding motif, but retains the ligand-binding domain characteristic of other family members (1). DAX-1 is expressed in the adrenal cortex, gonads, hypothalamus and anterior pituitary (2). It interacts with another orphan nuclear receptor, steroidogenic factor-1 (SF-1) (3), which plays a pivotal role in the development and function of these tissues (4-9). In vitro studies suggest that DAX-1 represses SF-1-mediated transcription, but the roles of SF-1 and DAX-1 in the development and function of these tissues remain unclear (5-7). Recent results obtained in Ahch (the mouse Dax1 homologue) knockout mice suggest that DAX-1 may also play a direct role in spermatogenesis (10).Mutations in the DAX1 gene in humans cause the Xlinked cytomegalic form of adrenal hypoplasia congenita (AHC), a rare disorder characterized by impaired development of the permanent zone of the adrenal cortex and hypogonadotropic hypogonadism (HHG) (1, 11). Affected boys develop adrenal failure shortly after birth or during early childhood, whereas HHG, a universal feature of the syndrome, is usually recognized at the expected time of puberty (9, 12, 13). Whether or not DAX1 mutations affect spermatogenesis in humans, independent of the effects of gonadotropin deficiency, remains unknown (9).In this report, we describe the clinical features of a patient with a mild phenotypic presentation of AHC and examine the functional properties of the mutant DAX-1 protein. In addition, we describe the results of exogenous gonadotropin therapy on spermatogenesis. Recognition of this unique phenotype is of practical importance because it extends the clinical spectrum of the disease to include mild forms of HHG and delayed onset of adrenal insufficiency. Studies in this patient also suggest that DAX-1 function is required for spermatogenesis in humans, independent of gonadotropin and testosterone production. Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). In affected boys, primary adrenal insufficiency occurs soon after birth or during early childhood; HHG is recognized at the expected time of puberty. In this report, we describe the novel phenotype of a man who presented with apparently isolated adrenal insufficiency at 28 years of age. Examination revealed partial pubertal development and undiagnosed incomplete HHG. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. Genomic analysis revealed a novel missense mutation, I439S, in DAX1. The mutant DAX-1 protein was studied for its ability to function as a transcriptional repressor of target genes. Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC. This unique case extends the clinical spectrum of AHC to include de...

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“…This is in contrast to the situation in man where LH levels tend to increase with age, presumably because of decreasing testosterone levels (Rubens et al, 1974;Vermeulen, 1978). In addition, the half-life of circulating LH in humans is in excess of 100 min (Caron et al, 1994), while in the rat the half life is 5 to 10 min (De Groot et al, 1995b), demonstrating that human LCs are exposed to higher physiologic levels of LH over their lifetime. The apparent lower spontaneous LCT incidence in man compared with the rat, despite greater exposure to LH, further suggests the relative insensitivity of human LCs to proliferative influences of LH.…”

Section: B Comparative Biologymentioning

confidence: 99%

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

Cook

Klinefelter

Hardisty

et al. 1999

Critical Reviews in Toxicology

175

122

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Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years because of its common occurrence in rodent bioassays and the importance in assessing the relevance of this tumor type to humans. To date, there have been no comprehensive reviews to identify all the compounds that have been shown to induce LCTs in rodents or has any review systematically evaluated the epidemiology data to determine whether humans were at increased risk for developing LCTs from exposure to these agents. This review attempts to fill these deficiencies in the literature by comparing the cytology and ontogeny of the LC, as well as the endocrine and paracrine regulation of both normal and tumorigenic LCs. In addition, the pathology of LCTs in rodents and humans is compared, compounds that induce LC hyperplasia or tumors are enumerated, and the human relevance of chemical-induced LCTs is discussed. There are plausible mechanisms for the chemical induction of LCTs, as typified by agonists of estrogen, gonadotropin releasing hormone (GnRH), and dopamine receptors, androgen receptor antagonists, and inhibitors of 5alpha-reductase, testosterone biosynthesis, and aromatase. Most of these ultimately involve elevation in serum luteinizing hormone (LH) and/or LC responsiveness to LH as proximate mediators. It is expected that further work will uncover additional mechanisms by which LCTs may arise, especially the role of growth factors in modulating LC tumorigenesis. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-testis (HPT) axis of rats and humans are similar, such that compounds that either decrease testosterone or estradiol levels or their recognition will increase LH levels. Hence, compounds that induce LCTs in rats by disruption of the HPT axis pose a risk to human health, except for possibly two classes of compounds (GnRH and dopamine agonists). Because GnRH and prolactin receptors are either not expressed or are expressed at very low levels in the testes in humans, the induction of LCTs in rats by GnRH and dopamine agonists would appear not to be relevant to humans; however, the potential relevance to humans of the remaining five pathways of LCT induction cannot be ruled out. Therefore, the central issue becomes what is the relative sensitivity between rat and human LCs in their response to increased LH levels; specifically, is the proliferative stimulus initiated by increased levels of LH attenuated, similar, or enhanced in human vs. rat LCs? There are several lines of evidence that suggest that human LCs are quantitatively less sensitive than rats in their proliferative response to LH, and hence in their sensitivity to chemically induced LCTs. This evidence includes the following: (1) the human incidence of LCTs is much lower than in rodents even when corrected for detection bias; (2) several ...

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Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis

Cited by 11 publications

References 13 publications

Perspectives in Pediatric Pathology, Chapter 22. Testicular Involvement in Systemic Diseases

Perspectives in Pediatric Pathology, Chapter 22. Testicular Involvement in Systemic Diseases

A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

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