Lack of effects of recombinant human GH on spermatogenesis in the adult cynomolgus monkey (Macaca fascicularis).
OBJECTIVE
The effects on male reproductive parameters after 1 year of treatment with recombinant human GH to the cynomolgus monkey were investigated.


METHODS
Twenty-four male cynomolgus monkeys were given daily subcutaneous doses of 0 (vehicle) (n=7), 0.4 (n=5), 2.0 (n=5) and 10.0 (n=7) IU/kg bodyweight for 52 weeks. At completion of the treatment period two control and two high-dose animals were left for a 12-week treatment-free period.


METHODS
Before and during the treatment period and during the recovery period, sperm analyses, testicular volume measurements and hormone analyses of prolactin (PRL), LH, FSH, testosterone and IGF-I in serum, and analysis of serum antibodies against human GH were performed. Testicular morphology was monitored by biopsies, predose and on day 15 of the study, and with light microscopy on organ samples collected at time of death, at the end of the treatment, and during recovery periods respectively.


RESULTS
Of all studied parameters, alterations were observed only in serum levels of IGF-I and PRL. IGF-I showed a dose-dependent increase throughout the treatment, with a normalisation during the treatment-free period. PRL decreased significantly in animals given 10.0IU/kg per day from week 14 of treatment and throughout the study but with a normalisation upon cessation of treatment. Spermatogenesis, as judged from semen analysis, testicular volume measurements and testicular morphology was not affected.


CONCLUSIONS
This controlled preclinical study demonstrates that high doses of human GH do not alter male reproductive parameters in a non-human primate model.
Sjögren
I
I
Toxicology, Pharmacia Upjohn, Stockholm, Sweden.
Ekvärn
S
S
Zühlke
U
U
Vogel
F
F
Bee
W
W
Weinbauer
G F
GF
Nieschlag
E
E
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D013076:Sperm Count / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D019382:Human Growth Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone