Reproductive responses of cattle to GnRH agonists

The response in cattle to treatment with gonadotrophin releasing hormone (GnRH) agonist includes downregulation of GnRH receptors on gonadotrophe cells, desensitisation of the anterior pituitary gland to endogenous GnRH, and the abolition of pulsatile release of LH. In bulls, a tonic pattern of LH release is associated with increased secretion of testosterone, which persists for the duration of treatment with GnRH agonist. The mechanism for this response in bulls has not been elucidated, but clearly pulsatile release of LH is not required to stimulate the synthesis of steroidogenic enzymes that sustain elevated secretion of testosterone. In heifers, desensitisation to endogenous GnRH prevents the occurrence of the pre-ovulatory surge release of LH, thus blocking ovulation. The latter provided the opportunity to evaluate the potential of a GnRH agonist bioimplant to control fertility in heifers under extensive management. Bioimplants that contained graded amounts of GnRH agonist prevented pregnancies in heifers for periods of 3 to 12 months. Zebu crossbred heifers treated with GnRH agonist from 14 to 23 months of age failed to conceive, but showed normal conception patterns when introduced into mating herds at around 26 months of age. After treatment with GnRH agonist for 4 to 6 weeks, ovarian follicular growth in heifers is restricted to relatively small (2-4 mm) antral follicles. Suppressed follicular growth in heifers treated long-term with GnRH agonist is due to a lack of gonadotrophin support, rather than a direct action of agonist at the ovaries. This was demonstrated by the ability to induce apparently normal follicular growth and ovulation by acute treatment with FSH for 4 days, followed by an injection of LH, in heifers that had been exposed to GnRH agonist for around 6 months, and which had only small (2-4 mm) antral follicles at the start of FSH treatment. GnRH agonist bioimplants have been incorporated into new multiple ovulation and embryo transfer protocols that allow control of the time of ovulation subsequent to superstimulation of ovarian follicular growth with FSH. In these protocols, the endogenous surge release of LH is blocked by treatment with agonist and ovulation is timed by injection of exogenous LH, allowing fixed-time AI. It can be concluded from recent studies that GnRH agonist bioimplants have considerable potential for both pro-fertility and anti-fertility applications in cattle. It is likely that commercial bioimplants will be available within the next 3 to 5 years.