A newborn boy is found to have micropenis at birth. Genetic analysis identifies a specific mutation in the NR5A1/SF-1 gene that results in selective impairment in Sertoli cell function. The remainder of the hypothalamic-pituitary-gonadal axis is unaffected. The patient undergoes regular follow-up with a pediatric endocrinologist during childhood and has otherwise normal childhood and pubertal development. When he is 16 years old, serum hormone levels are obtained. Which of the following patterns of blood hormone levels are most likely to be seen as a result of this patient's condition?

Question

Quizplus · Accepted Answer

11ec160b_3ccd_bcca_9249_33d33977b721_MD0001_00 Sertoli and Leydig cells are the hormone-producing cells of the testis. Leydig cells, which are analogous to female theca cells, produce testosterone in response to stimulation by luteinizing hormone. LH is released from the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. Testosterone causes feedback inhibition of both LH and GnRH release. Sertoli cells, which are analogous to female granulosa cells, produce the hormone inhibin in response to FSH from the anterior pituitary. Inhibin suppresses FSH production by the anterior pituitary, although it does not feed back on the hypothalamus. Sertoli cells also facilitate spermatogenesis within the seminiferous tubules. Steroidogenic factor-1 (SF-1) is a nuclear receptor that regulates the transcription of several genes involved in steroidogenesis, sexual development, and reproduction. Mutations of SF-1/NR5A1 cause a wide variety of phenotypic features in males and females, including genital malformations and Sertoli cell failure. Selective impairment in Sertoli cell function would cause decreased production of inhibin and lead to increased FSH levels (Choice D), as well as infertility due to impaired sperm production. However, the Leydig cells are unaffected, so no changes in testosterone or LH levels would be expected. (Choice A) Decreased release of all of these hormones is a sign of anterior pituitary failure, which can occur with Kallmann syndrome, sellar mass lesions, pituitary apoplexy, or radiation injury. (Choice B) This pattern would be observed if the Leydig cells were selectively impaired. Isolated Leydig cell failure has been reported in patients with LH/hCG receptor defects on Leydig cells. (Choice E) Most pituitary adenomas arising from gonadotrophs produce only the biologically inactive alpha subunit (nonfunctioning adenomas), although adenomas producing intact FSH are occasionally seen. Inhibin levels may be either normal or elevated. Males with FSH-secreting adenomas are usually asymptomatic, but some will have enlargement of the testes. Educational objective: Sertoli cells produce inhibin in response to FSH from the anterior pituitary. Inhibin suppresses FSH production in the pituitary. Sertoli cells also facilitate spermatogenesis within the seminiferous tubules. Impaired Sertoli cell function would lead to decreased production of inhibin, increased FSH levels, and impaired fertility. __________ References: Predominant Sertoli cell deficiency in a 46,XY disorders of sex development patient with a new NR5A1/SF-1 mutation transmitted by his unaffected father. (http://www.ncbi.nlm.nih.gov/pubmed/21163476)

A Newborn Boy Is Found to Have Micropenis at Birth