1. Brian S. Edwards1, Cheryl S. Asa2, Donal C
Brian S. Edwards1, Cheryl S. Asa2, Donal C. Skinner1 1Neuroscience Program and Department of Zoology and Physiology, University of Wyoming, 1000 E Univ. Ave., Dept. 3166, Laramie, WY 82071, USA 2Research Department, Saint Louis Zoo, 1 Government Drive, Saint Louis, MO 63110, USA
#28
Short term exposure of a high dose GnRH agonist and its effects on
gonadotropin secretion in the anterior pituitary of adult male rats
BSN
2011
Introduction
Materials and Methods
GnRH agonists are used in an array of therapies for steroid-dependent diseases, most notably prostate cancer (Chillik and Acosta, 2001), and are also used as an alternative to surgical castration (Kauffold et al., 2010). These agonists are reported to work by down-regulating the GnRH-receptor, which subsequently reduces LH and FSH production in the pituitary gland (Bubley, 2001).
Evidence in humans suggests that persistent exposure to GnRH agonists may cause permanent hypothalamo-pituitary changes. We investigated the ability of the male rat pituitary gland to recover from a chronic exposure to an extremely high dose of the GnRH agonist, deslorelin.
Adult Male Sprague Dawley rats (185.2 ± 0.4 days) were implanted with 14.1 mg deslorelin (Suprelorin; Peptech Animal Health) for 44.4±0.4 days. Rats were then killed immediately (n=7), or after 4 (n=6) or 12 (n=5) weeks recovery. Another group (n=7) was treated with 14.1mg deslorelin plus a 15mg testosterone (T) implant. Controls included sham implanted rats (n=5) and rats (n=6) coinciding with the 12 week recovery. Pituitaries were fixed via transcardial perfusion and sagittally sectioned (20µm). Pituitary sections were immuno-labeled for FSHβ and LHβ to determine the percentage and density of gonadotropes. Plasma was obtained via cardiac puncture and FSH, LH and T were estimated by RIA or EIA.
Results
Control
Deslorelin
Deslorelin + Testosterone
Deslorelin + 4 wk recovery
Deslorelin + 12 wk recovery
12 wk control
FSHβ
LHβ
Control vs. treated groups *(P < 0.05) or *** (P < 0.001)
Desl vs. Desl + T †† (P < 0.01) or ††† (P < 0.001)
Mono-FSHβ
Mono-LHβ
Testes
Epididymis
Bi-hormonal
*** *
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†††
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Conclusions
High dose deslorelin significantly reduced LHβ- and FSHβ-immunoreactive gonadotropes - recovery was evident within 4 weeks of implant removal
Plasma FSH and testosterone concentrations were significantly reduced by deslorelin, while LH was unaffected.
Testosterone did not change the proportion of immunoreactive gonadotropes but it altered the expression of the β.
However, testosterone replacement restored plasma FSH concentrations and increased FSHβ-immunoreactive gonadotropes to ~50% of control values.
In contrast, testosterone enhanced the suppressive effect of deslorelin on LHβ-immunoreactive gonadotropes but had no effect on plasma LH concentrations
Groups containing different letters in the individual graphs are significantly different from each other (P<0.05)
Bubley GJ. Urology; 2001; 58(suppl 1): 5-9.
Chillick C, Acosta A. Reprod Biomed Online. 2001; 2(2):
Kauffold J, Hartmut R, Boehm J, Wehrend A. Theriogenology; 2010; 74:
References
Supported by NIH Grant, P20RR015640