Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency

Hiroyuki Ono, Chikahiko Numakura, Keiko Homma, Tomonobu Hasegawa, Seiji Tsutsumi, Fumiko Kato, Yasuko Fujisawa, Maki Fukami, Tsutomu Ogata

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Although POR deficiency (PORD) is assumed to be accompanied by excessive placental androgen accumulation and enhanced adrenal and testicular androgen production via the backdoor pathway as well as compromised testicular androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental androgens into the fetal circulation and for the production of dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum androstenedione and testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway.

Original languageEnglish
JournalJournal of Steroid Biochemistry and Molecular Biology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Antley-Bixler Syndrome Phenotype
Dihydrotestosterone
Metabolites
Steroids
Urine
Androgens
Serum
Parturition
Mothers
Synostosis
Virilism
Pregnancy
Androstenedione
Puberty
Radio
Testosterone
Testis
Chemical activation
Fluxes

Keywords

  • Backdoor pathway
  • Disorders of sex development
  • Frontdoor pathway
  • Placental androgen
  • POR deficiency
  • Steroid profile

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency. / Ono, Hiroyuki; Numakura, Chikahiko; Homma, Keiko; Hasegawa, Tomonobu; Tsutsumi, Seiji; Kato, Fumiko; Fujisawa, Yasuko; Fukami, Maki; Ogata, Tsutomu.

In: Journal of Steroid Biochemistry and Molecular Biology, 01.01.2018.

Research output: Contribution to journalArticle

Ono, Hiroyuki ; Numakura, Chikahiko ; Homma, Keiko ; Hasegawa, Tomonobu ; Tsutsumi, Seiji ; Kato, Fumiko ; Fujisawa, Yasuko ; Fukami, Maki ; Ogata, Tsutomu. / Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency. In: Journal of Steroid Biochemistry and Molecular Biology. 2018.
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AU - Ono, Hiroyuki

AU - Numakura, Chikahiko

AU - Homma, Keiko

AU - Hasegawa, Tomonobu

AU - Tsutsumi, Seiji

AU - Kato, Fumiko

AU - Fujisawa, Yasuko

AU - Fukami, Maki

AU - Ogata, Tsutomu

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