Disease relevance of Hypogonadism

• The recently identified gene for X-linked Kallmann syndrome (hypogonadotropic hypogonadism and anosmia) has a closely related homologue on the Y chromosome [1].
• Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta-subunit gene [2].
• We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism [3].
• Juvenile hemochromatosis is an early-onset autosomal recessive disorder of iron overload resulting in cardiomyopathy, diabetes and hypogonadism that presents in the teens and early 20s (refs. 1,2) [4].
• Analogues of gonadotropin-releasing hormone (GnRH) are often given to induce hypogonadism in women who have estrogen-dependent disorders such as endometriosis and uterine leiomyomas [5].

Psychiatry related information on Hypogonadism

• We identified a homozygous missense mutation in the noncatalytic subunit (RAB3GAP2) of RAB3GAP that results in abnormal splicing in a family with congenital cataracts, hypogonadism, and mild mental retardation (Martsolf syndrome) [6].
• Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction [7].
• At a dedicated renal impotence clinic, we studied the effectiveness of testosterone replacement in men with biochemically proven hypogonadism and then vacuum tumescence therapy in those with continued erectile dysfunction [8].
• Prolactin levels are necessary only in patients with hypogonadism and/or a history of decreased libido [9].
• In a series of 70 men with vertebral crush fractures, 38 (54%) were found to have an underlying secondary cause of osteoporosis such as hypogonadism (16%), oral steroid therapy (13%), neoplastic disease (9%), excess alcohol consumption (6%), gastric surgery (1%) or a combination of these factors (10%) [10].

High impact information on Hypogonadism

• Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism [11].
• The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans [12].
• Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene [13].
• Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism [14].
• A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor [15].

Chemical compound and disease context of Hypogonadism

• Treatment with GnRH reversed the hypogonadism and restored fertility in each of the five men who received long-term therapy [16].
• Brief report: melatonin-related hypogonadotropic hypogonadism [17].
• Hypogonadotropic hypogonadism (HHG) is frequently associated with this disorder but is thought not to be caused by the low adrenal androgen levels due to adrenal hypoplasia [18].
• Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established [19].
• BACKGROUND: Both hypogonadism and low estrogen levels adversely affect bone health in young men [20].

Biological context of Hypogonadism

• The association of hypogonadism with bone mineral density was examined with adjustment for confounders, including estradiol levels [20].
• The effect of long-term administration of gonadotropin-releasing hormone (GnRH) for induction and maintenance of sexual maturation was characterized in 23 men with idiopathic hypogonadotropic hypogonadism [21].
• Hemochromatosis, hypogonadism, testosterone, and erythropoiesis [22].
• The phenotype of the Pkr2(-/-) mice showed similarity to the clinical features of Kallmann syndrome, a human disease characterized by association of hypogonadotropic hypogonadism and anosmia [23].
• Mutations in the DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome; NR0B1] gene cause X-linked AHC associated with hypogonadotropic hypogonadism [24].

Anatomical context of Hypogonadism

• Intrahypothalamic injection of a cell line secreting gonadotropin-releasing hormone results in cellular differentiation and reversal of hypogonadism in mutant mice [25].
• Gonadotropin-releasing hormone (GnRH) receptor mutants from patients with hypogonadotropic hypogonadism are frequently misrouted proteins that exert a dominant-negative (DN) effect on human (h) wild-type (WT) receptor, due to oligomerization and retention in the endoplasmic reticulum [26].
• It is more likely that the astrocyte response in the MBH in hpg mice reflects permanent differences in steroid-induced neuronal connectivity, caused by the hypogonadism [27].
• Moreover, the relationship of hypogonadism with quadriceps muscle weakness and exercise intolerance has been studied scarcely in men with COPD [28].
• The expression of DAX-1 in the neuroendocrine system suggests that interruption of the expression in these tissues may be the cause of the hypogonadotropic hypogonadism (HH) that is frequently associated with AHC [29].

Gene context of Hypogonadism

• In man, disrupted GnRH neuronal ontogeny can be caused by several monogenic disorders leading to isolated hypogonadotrophic hypogonadism (IHH); these include mutations within KAL-1, GnRH-R, and FGFR1 [30].
• Mutations in the human DAX1 gene (also known as AHC) cause the X-linked syndrome AHC, a disorder that is associated with hypogonadotropic hypogonadism also [31].
• Juvenile hemochromatosis is an early-onset form of iron storage disease characterized by hypogonadotrophic hypogonadism and cardiomyopathy [32].
• Male and female mice deficient in Fancg showed hypogonadism and impaired fertility, consistent with the phenotype of FA patients [33].
• Both male and female mice homozygous for Fanca mutation exhibit hypogonadism, and homozygous females demonstrate premature reproductive senescence and an increased incidence of ovarian cysts [34].

Analytical, diagnostic and therapeutic context of Hypogonadism

• Since idiopathic hypogonadotropic hypogonadism is thought to represent a disorder of gonadotropin-releasing-hormone (GnRH) secretion, we used long-term low-dose subcutaneous GnRH, administered in an episodic fashion by a portable infusion pump, in an effort to establish a normal adult pattern of gonadotropin secretion in six men [35].
• DESIGN: Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design [36].
• INTERVENTION: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing-hormone (GnRH) antagonist, Nal-Glu, for 6 weeks [37].
• Treatment of primary hypogonadism in men by the transdermal administration of testosterone [38].
• In the 7 patients with postpubertal hypogonadism, treatment with hCG alone for 6 months increased the serum testosterone concentration and maximum sperm count to normal, even though the previously normal inhibin concentration was not increased further [39].

References