Table 3 Time of onset of the LH surge relative to progesterone withdrawal in intact control ewes and those treated with
insulin, with or without additional naloxone or RU486 Ž
. Treatment
Onset of LH surge hours after P withdrawal
a
Ž .
Control ns9 627
b
Ž .
Insulin alone 5 IUrkg at 38 and 40 h; ns13 761
Insulinqnaloxone infusion
a
Ž .
1 mg naloxonerkgrh for 12 h starting at 37 h; ns 5 615
b
Ž .
InsulinqRU486 1 injection of 100 mg at 37 h; ns 4 784
a
Ž .
Significantly different from insulin alone group P - 0.05 .
b
Ž .
Significantly different from control group P - 0.05 .
of two neurotransmitter regulators, and the preliminary results are very interesting. Infusion of the opioid antagonist, naloxone just before insulin administration prevented
Ž .
the delay in the onset of the LH surge observed after insulin alone Table 3 . This clearly implicates opioids in the mediation of stress-induced changes in LH secretion.
Furthermore, it would appear that progesteronerglucocorticoid receptors are not in- volved in the interaction between the stress and reproductive axes because the antagonist
Ž .
RU486 was unable to reverse the insulin-induced delays in the LH surge Table 3 .
6. The link between stress-induced low LH pulse frequency and cases of subfertility
Within the growing follicle, the oocyte maintains direct contact with granulosa cells Ž
. by means of cellular projections through the zona pellucida Moor et al., 1980 . Thus,
events influencing the integrity of follicular function can have direct effects on oocyte viability. These effects are not always immediately obvious, for example, it is known
that mRNAs are laid down in the oocyte nucleus but not translated until the 8-cell stage
Ž .
of conceptus development Staigmiller and Moor, 1984 . Consequently, any event that changes granulosa cell activity may influence pregnancy rates. Indeed, Mihm et al.
Ž .
1994 have provided evidence for reduced pregnancy rates after prolonging the duration of the follicular phase by artificially delaying the onset of the LH surge.
It is envisaged that in some situations, such as during the chronic stress of more severe lameness or fever, the pulse GnRHrLH frequency will be so slow that initial
follicular growth will occur but will be unable to continue in to the later stages that depend on faster pulse frequencies. Thus, the animal fails to maintain oestrous cycles
and the consequent anoestrus is easily recognised by veterinarians.
In slightly less stressful situations, GnRHrLH pulse frequency may be just fast enough to support follicular growth, but because it is on a knife-edge, it will be
susceptible to interruption or variation by otherwise innocuous stimuli. In this case, the integrity of granulosa cells and thus the oocyte may be compromised, and although
oestrus and fertilisation may occur, the conceptus will fail to develop into a pregnancy. This is reflected in the insidious idiopathic subfertility recognised by agricultural
advisers and veterinarians.
A third scenario could exist in which pulse frequency is sufficient to get a follicle into the later stages of development but is not quite fast enough to provide correct
GnRH priming of the pituitary andror adequate oestradiol production. Hence, an inappropriate LH surge is generated and, as it is unable to cause ovulation and
luteinisation, the follicle persists to produce the clinically recognised cystic ovarian syndrome.
7. Conclusion
