Opioidergic, dopaminergic and adrenergic regulation of LH secretion in prepubertal heifers.

Abstract

Studies have shown inhibitory effects of endogenous opioids on LH secretion in early post-natal heifers. However, it is not clear whether these effects change during the rest of the prepubertal period or whether the inhibitory influences on the GnRH neurones are direct or by way of other neuronal systems. Two experiments were performed in heifer calves to study the developmental patterns of opioidergic, dopaminergic and adrenergic regulation of LH and the possible interactions between opioids and dopaminergic and adrenergic neuronal systems, in the regulation of LH secretion. In Expt 1 four groups each of five heifer calves were used. Blood samples were taken every 15 min for 10 h and each calf received one of the following treatments as a single injection at 4, 14, 24, 36 and 48 weeks of age: (i) naloxone (opioid antagonist, 1 mg kg(-1), i. v.); (ii) sulpiride (dopamine D2 antagonist, 0.59 mg kg(-1), s.c.); (iii) naloxone and sulpiride combined; or (iv) vehicle (control group). Treatments began after the first blood sample was taken. The design of Expt 2 was similar; a separate group of heifer calves was assigned to receive one of the following treatments as a single injection at 4, 14, 24, 36 and 48 weeks of age: (i) naloxone; (ii) phenoxybenzamine (an alpha-adrenoreceptor blocker, 0.8 mg kg(-1), i. v.); (iii) naloxone and phenoxybenzamine; (iv) or vehicle. Results from Expt 1 showed that the maximum concentration of LH and the number of calves responding to treatments with an LH pulse was higher in the first hour after treatments at 36 and 48 weeks of age in the naloxone group compared with the control or sulpiride groups (P < 0.05). These values in the naloxone group also increased over time and were greatest at 48 weeks of age (P < 0.05). In heifers given naloxone + sulpiride treatment at 36 and 48 weeks of age, maximum concentrations of LH in the first hour after treatment did not differ from the naloxone and control groups. In Expt 2, at 36 and 48 weeks of age, treatment with naloxone with or without phenoxybenzamine resulted in higher concentrations of LH than in the controls (P < 0.05). No pulses were seen over the first hour of treatment at 36 and 48 weeks of age in heifers treated with phenoxybenzamine. The 10 h periods of blood sampling at 48 weeks of age revealed that phenoxybenzamine alone suppressed LH pulse frequency and mean serum concentrations of LH compared with the control group (P < 0.05). It was concluded that a strong or more acute inhibition of LH secretion by endogenous opioids developed in mid- to late prepubertal heifers, or alternatively, that removal of opioidergic inhibition at the GnRH neurone unmasked stimulatory inputs that were greater in heifers close to first ovulation. Since sulpiride appeared to negate in part the effects of naloxone on LH release, the suppressive effects of opioids could be exerted in part through the inhibition or blocking of a stimulatory dopaminergic system. alpha-Adrenergic neuronal systems have stimulatory effects on LH release, especially during the late prepubertal period, but do not appear to mediate opioidergic inhibition of LH secretion in prepubertal heifer calves.