Male Reproductive Endocrinology: When to Replace Gonadotropins

Jc, Trussell

doi:10.1055/s-0033-1345270

Cited by 13 publications

(8 citation statements)

References 52 publications

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“…In primary hypogonadism, testicular function is compromised, and in response the anterior pituitary releases above normal levels of LH/FSH in an attempt to increase output from Sertoli and Leydig cells (35). Gonadal steroid hormone production is an enzymatically mediated process catalyzed by several enzymes from two main categories: the cytochrome P450 enzymes (CYP11A and CYP17A) and HSD enzymes (3␤-HSD and 17␤-HSD) (26).…”

Section: Discussionmentioning

confidence: 99%

Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice

Sun

Chen

Zhang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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We used mice with targeted deletion of 25-hydroxyvitamin D-1 α-hydroxylase [1α(OH)ase(-/-)] to investigate whether 1,25(OH)2D3 deficiency results in male infertility mediated by 1,25(OH)2D3 or extracellular calcium and phosphorus. Male 1α(OH)ase(-/-) and their wild-type littermates fed either a normal diet or a rescue diet from weaning were mated at 6-14 wk of age with female wild-type mice on the same diet. The fertility efficiency of females was analyzed, and the reproductive phenotypes of males were evaluated by histopathological and molecular techniques. Hypocalcemic and hypophosphatemic male 1α(OH)ase(-/-) mice on a normal diet developed infertility characterized by hypergonadotropic hypogonadism, with downregulation of testicular calcium channels, lower intracellular calcium levels, decreased sperm count and motility, and histological abnormalities of the testes. The proliferation of spermatogenic cells was decreased with downregulation of cyclin E and CDK2 and upregulation of p53 and p21 expression, whereas apoptosis of spermatogenic cells was increased with upregulation of Bax and p-caspase 3 expression and downregulation of Bcl-xl expression. When serum calcium and phosphorus were normalized by the rescue diet, the defective reproductive phenotype in the male 1α(OH)ase(-/-) mice, including the hypergonadotropic hypogonadism, decreased sperm count and motility, histological abnormalities of testis, and defective spermatogenesis, was reversed. These results indicate that the infertility seen in male 1,25(OH)2D3-deficient mice is not a direct effect of active vitamin D deficiency on the reproductive system but is an indirect effect mediated by extracellular calcium and phosphorus.

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Section: Discussionmentioning

confidence: 99%

Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice

Sun

Chen

Zhang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…The endocrine definition of HH varies, but the classical definition, which includes Kallman's syndrome and IHH, is generally accepted as FSH < 2.5 IU/L and LH values of <2.5 IU/L with concomitant hypogonadism [8]. This strict definition does not account for the more common forms of HH in men, men with a low bioavailable testosterone (<155 ng/dL) and an inappropriately low LH (<5 IU/ L).…”

Section: Hypogonadotropic Hypogonadismmentioning

confidence: 99%

Hormone-Based Treatments in Subfertile Males

2016

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Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments.

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“…If low intratesticular testosterone (ITT) is a suspected aetiology, which would be suggested by low serum testosterone levels, LH levels are examined to help differentiate between hypogonadotropic hypogonadism (low LH, low T) vs. primary hypogonadism (high LH, low T). Hypogonadotropic hypogonadism is the rarer of the two entities and is associated with Kallman syndrome, idiopathic hypogonadotropic hypogonadism and congenital adrenal hyperplasia (Duke et al ., ; Layman et al ., ; Trussell, ). In the case of hypogonadotropic hypogonadism, treatment is directed towards stimulation of the Leydig cell through the LH receptor by pharmacologic means [recombinant LH, hCG, pulsatile gonadotropin releasing hormone (GnRH), or clomiphene], the objective is to correct putative low intratesticular testosterone levels and thus restore spermatogenesis (Hamada et al ., ).…”

Section: Introductionmentioning

confidence: 99%

“…Hypogonadism has been shown to be associated with non‐obstructive azoospermia in as many as 47% of patients undergoing testicular sperm extraction, and therefore means by which to modulate testosterone levels have been areas of extreme interest (Ramasamy et al ., ). Unfortunately, treatment with exogenous LH/hCG/clomiphene in individuals with primary hypogonadism is often ineffective in stimulating Leydig cell testosterone production to raise serum and intratesticular testosterone levels (Bremner et al ., ; Zwart et al ., ; Hussein et al ., ; Reifsnyder et al ., ; Trussell, ). Moreover, the exogenous administration of testosterone itself, although it increases serum testosterone levels, is unlikely to increase intratesticular testosterone levels.…”

Section: Introductionmentioning

confidence: 99%

“…In the case of hypogonadotropic hypogonadism, treatment is directed towards stimulation of the Leydig cell through the LH receptor by pharmacologic means [recombinant LH, hCG, pulsatile gonadotropin releasing hormone (GnRH), or clomiphene], the objective is to correct putative low intratesticular testosterone levels and thus restore spermatogenesis (Hamada et al ., ). Primary hypogonadism, the more common entity, can be more challenging to manage, but some may still respond to LH receptor stimulation (Hussein et al ., ; Trussell, ; Hotaling & Patel, ).…”

Section: Introductionmentioning

confidence: 99%

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New targets for increasing endogenous testosterone production: clinical implications and review of the literature

Chen

Zirkin

et al. 2014

Andrology

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SUMMARYOver the past several decades, our understanding of the regulatory mechanisms of testosterone production has increased significantly. Concurrently, the medical treatment of hypogonadism, particularly in the ageing male has increased. This review article consolidates some of our insights into the regulatory mechanisms of endogenous testosterone production and examines promising new targets that may allow endogenous production of testosterone to be re-established in males with primary hypogonadism. We examined the published scientific literature regarding regulatory mechanisms of testosterone biosynthesis with a focus on Leydig cell physiology and small-molecule regulation that resulted in increased testosterone production. We identified several pathways that have been manipulated pharmacologically to increase Leydig cell testosterone production, including phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin. Manipulation of these pathways with small molecules has helped further our understanding of the regulatory pathways of testosterone biosynthesis. Herein, we identified five future targets that might promote increased endogenous testosterone production through the Leydig cell instead of relying on exogenous testosterone administration.

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Male Reproductive Endocrinology: When to Replace Gonadotropins

Cited by 13 publications

References 52 publications

Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice

Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice

Hormone-Based Treatments in Subfertile Males

New targets for increasing endogenous testosterone production: clinical implications and review of the literature

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