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GnRH receptor blockage alters the activity of the reproductive axis in male and female sheep

GnRH receptor blockage alters the activity of the reproductive axis in male and female sheep

Patients with early onset GID are treated chronically with a GnRH receptor agonist to delay puberty, however the effects of such treatment on physiology, behaviour and cognition are unclear. To explore these an animal model of GID was established using sheep given monthly implants of the GnRH agonist goserelin acetate (Zoladex; 3.6mg) from immediately prior to puberty.

(male; 8 weeks: female; 28 weeks) until they were euthanized at 11 months of age. GnRH treatment (T) did not alter body weight, however it reduced the weights of the gonads compared to controls (C). Testes: C, n=21, 76.01± 3.67g; T, n=20, 55.55 ± 4.49g, p=0.002. Ovaries: C, n=20, 0.69 ± 0.04g; T, n=20, 0.55 ± 4.49, p=0.004. The number of immunoreactive GnRH neurones was also significantly (p=0.04) reduced in the T animals. Although the weights of the pituitary glands was not altered by treatment in either sex the cellular populations were altered.
Specifically, GnRH agonist treatment altered the proportion of gonadotrophs expressing oestrogen receptor alpha (ERa) in a sex specific manner. Thus, the percentage of gonadotrophs co-localising ERa was lower in the treated females (p=0.001) but did not differ in the males. Further, the percentage of ERa immunoreactive pituitary cells was reduced by GnRH agonist treatment in both sexes (p=0.001).
In summary, long term treatment with a GnRH agonist affects all levels of the reproductive axis and provides us with an excellent animal model to explore other physiological, behavioural and cognitive processes that might be altered by such long term exposure.

Speakers: Jane E Robinson
Conference: WAS Glasgow 2011