Urinary cysteinyl progestogens: Occurrence and origin.
The presence of two cysteinyl progestogens, 16-cysteinyl-progesterone (16-Cys-Prog) and 16-cysteinyl-pregnenolone (16-Cys-Preg), in human urine is described for the first time. Their occurrence was unequivocally confirmed by comparison with synthesized material by using mass spectrometric detectors. Several experiments were performed in order to clarify their origin. The adrenal origin of both 16-Cys-Prog and 16-Cys-Preg can be inferred from the increase in their concentrations after ACTH stimulatory test, together with their circadian variation similar to the one observed for cortisol. Moreover, the notable increase in excretions of 16-Cys-Prog during the luteal phase of the menstrual cycle points towards an ovarian production for this progestogen. However, the analysis of samples during the course of two pregnancies revealed that, in spite of the large amounts of progesterone produced during gestation, the human placenta lacks the capacity to make 16-Cys-Prog. The adrenal and ovarian origin has been further indicated by the absence of both metabolites in samples collected from a subject with bilateral adrenalectomy and hypogonadotrophyic hypogonadism. Regarding liver action, in vitro studies with hepatocytes and progesterone indicate that, although the liver is able to metabolize progesterone to 6-dehydroprogesterone, it has not the enzymatic machinery for the generation of 16-dehydroprogesterone. Taken together, these results open the possibility for a noninvasive test for the simultaneous evaluation of progesterone biosynthesis in different organs.
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain.
Josep
J
Marcos
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain.
Marta
M
Pol
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain.
Andreu
A
Fabregat
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain.
Rosa
R
Ventura
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain.
Nuria
N
Renau
Department of Endocrinology and Nutrition, Hospital Clinic, Laboratory of Endocrine Disorders, IDIBAPS, University of Barcelona, Barcelona, Spain.
Felicia A
FA
Hanzu
Biochemistry and Molecular Genetics Department, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
Gregori
G
Casals
Biochemistry and Molecular Genetics Department, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
Santi
S
Marfà
Servei d'Anàlisis Cliniques Hospital Universitari Son Espases, Palma de Mallorca, Spain.
Bernardí
B
Barceló
Servei d'Anàlisis Cliniques Hospital Universitari Son Espases, Palma de Mallorca, Spain.
Antonia
A
Barceló
Servei d'Anàlisis Cliniques Hospital Universitari Son Espases, Palma de Mallorca, Spain.
Juan
J
Robles
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain.
Jordi
J
Segura
Bioanalysis Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain. Electronic address: opozo@imim.es.
Oscar J
OJ
Pozo
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D045744:Cell Line, Tumor; D002648:Child; D003545:Cysteine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008183:Luteal Phase; D008297:Male; D010053:Ovary / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000652:urine; D011374:Progesterone / Q000031:analogs & derivatives* / Q000652:urine; D011372:Progestins / Q000652:urine*
C000601828:16-cysteinyl-pregnenolone; C000601827:16-cysteinyl-progesterone; D011372:Progestins; D011374:Progesterone; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D003545:Cysteine; D006854:Hydrocortisone
Adrenal glands; Cysteinyl; Gonads; Mass spectrometry; Placenta; Progestogen