The pituitary-testicular axis in Klinefelter's syndrome and in oligo-azoospermic patients with and without deletions of the Y chromosome long arm.
OBJECTIVE
The most frequent known genetic causes of severe oligospermia (< 5 million sperm/ml) or azoospermia in men are Klinefelter's syndrome (KS), and deletions in the Y chromosome long arm (Yq). We aimed to compare the function of the pituitary-testicular axis in patients with severe oligospermia or azoospermia, idiopathic or associated with Y chromosome deletions or Klinefelter's syndrome (KS) and in control subjects.


METHODS
We studied 47 men with idiopathic oligo-azoospermia, 42 with Yq deletions (27 AZFc, 13 AZFb and two AZFa) and oligo-azoospermia, 14 with KS and 39 control subjects (total 143).


METHODS
We analysed levels of FSH, inhibin-B, LH, free testosterone and oestradiol in all subjects, and we calculated indexes based on those hormones.


RESULTS
Inhibin-B levels were indistinguishable between patients with idiopathic and Y deletion-associated oligo-azoospermia, lowest in the Klinefelter's patients and highest in controls. FSH levels followed the reverse pattern: indistinguishable between patients with idiopathic and deletion-associated oligo-azoospermia, highest in Klinefelter's patients and lowest in controls. Oestradiol, free testosterone and the derived indeces were not different in subjects with Yq deletions compared to those with idiopathic oligo-azoospermia. Among the Yq-deleted patients, no measured or derived parameter differed between the subjects with AZFc deletion and those with AZFb deletion. When non-KS oligo-azoospermic patients were classified according to histology [Sertoli cell-only (SCO), n = 18 or non-Sertoli cell only (non-SCO), n= 18] and compared to KS patients, the hormonal pattern did not differ between SCO and non-SCO subjects, but levels in KS patients were significantly different for FSH, inhibin-B and the FSH/inhibin-B ratio. KS patients not only had lower inhibin-B than SCO and non-SCO oligo-azoospermic men, but also higher FSH levels for any given inhibin-B concentration.


CONCLUSIONS
Our data show that Y-deleted patients do not have a lesser impairment of Sertoli cell function than patients with idiopathic oligo-azoospermia, and support the concept that the main determinant of inhibin-B production is the germ cell mass. Also, our results suggest that one or more other factors, apart from inhibin-B, may contribute to increased pituitary secretion of FSH in KS patients.
Tomasi
Paolo A
PA
Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, 02142, USA. tomasi@ssmain.uniss.it
Oates
Robert
R
Brown
Laura
L
Delitala
Giuseppe
G
Page
David C
DC
D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D041322:Chromosomes, Human, Y; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D017353:Gene Deletion; D006801:Humans; D007265:Inhibins / Q000097:blood; D007713:Klinefelter Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D009845:Oligospermia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
C422364:inhibin B; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone