Prolactin Short-Loop Feedback and Prolactin Inhibition of Luteinizing Hormone Secretion during the Breeding Season and Seasonal Anoestrus in the Ewe

Abstract

In seasonally breeding mammals, plasma prolactin (PRL) concentrations vary on an annual basis with levels high in summer and low in winter. In this study of the ewe, we determined, first, whether PRL secretion is regulated by short-loop feedback and, second, whether the high summer levels of PRL are due to a change in sensitivity or loss of this feedback loop. Because the high summer levels of PRL coincide with the period of seasonal anoestrus in the ewe and could therefore be involved in the seasonal suppression of gonadotrophins, the effects of intracerebroventricular PRL on pulsatile LH secretion were also determined. Ovary intact ewes received intracerebroventricular injections of ovine PRL (oPRL; 50 µg) or anti-PRL serum. From 3 to 13 h after central administration of oPRL, plasma PRL concentrations were significantly reduced compared with the vehicle-treated controls. In contrast, following injection of anti-PRL serum, plasma PRL levels increased significantly. To determine whether there was a seasonal change in sensitivity to PRL feedback, a series of experiments were conducted in July and November when PRL concentrations are high and low, respectively. At each time of year, ovariectomized oestradiol-implanted ewes were injected intra-cerebroventricularly with 10 and 50 µg oPRL with control animals receiving the vehicle. At both times of year there was clear evidence of PRL short-loop feedback with no indication that sensitivity was reduced in the July trial. Luteinizing hormone (LH) pulse frequency, pulse amplitude and mean LH were not affected by intracerebroventricular oPRL at either time of year. These results indicate that the high PRL concentrations of summer are not due to the absence of PRL short-loop feedback and that suppression of pulsatile LH secretion during seasonal anoestrus is unlikely to be due to inhibition by PRL.

Prolactin Replacement Fails to Inhibit Reactivation of Gonadotropin Secretion in Rams Treated with Melatonin under Long Days

“…In addition, the LH response to NMDA was reduced in the same manner in both melatonin-treated groups, as occurs in sexually active rams [36], confirming that the exogenous PRL had not modified the central mechanisms regulating GnRH secretion. These results are also consistent with previous findings that the acute intracerebral ventricular (icv) injection of ovine PRL does not affect pulsatile LH secretion in ovariectomized, estradiol-implanted ewes [44], and the chronic icv infusion of ovine PRL in sexually active Soay rams is also ineffective at suppressing gonadotropin secretion [33].…”

Prolactin Cycles in Sheep under Constant Photoperiod: Evidence That Photorefractoriness Develops Within the Pituitary Gland Independently of the Prolactin Output Signal

“…This was evident as a posttreatment rebound increase in blood PRL concentrations, occurring when the control animals were becoming photorefractory to long days. This increase in PRL secretion is unlikely to result from a homeostatic response governed by the hypothalamus [35], because the HPD lesion disrupts the hypothalamic control, as confirmed by the absence of a PRL response to the dopamine-receptor antagonist, sulpiride, in experiment 2. The rebound response is also unlikely to result from parallel changes in other endocrine systems induced by the chronic bromocriptine (e.g., gonadal steroid secretion), because FSH secretion was blocked (as expected in the HPD rams) and because no evidence of androgen secretion was found (sex skin coloration was absent throughout).…”

“…This confirms that HPD surgery blocks the circadian control of PRL release. In addition, this indicates that the hypothalamic dopaminergic and adrenergic mechanisms that regulate PRL secretion may relay input from the circadian pacemaker system located in the suprachiasmatic nuclei to control the diurnal PRL rhythm as well as provide for the homeostatic control through the positivefeedback effect of PRL [1,35]. The lack of a short-term, 1:1 relationship between blood PRL and melatonin concentrations throughout the 24-h cycle in the HPD rams illustrates that melatonin does not act directly to control the photoperiod-induced changes in PRL secretion.…”

Evidence that Melatonin Acts in the Pituitary Gland through a Dopamine‐independent Mechanism to Mediate Effects of Daylength on the Secretion of Prolactin in the Ram

“…Thus photoperiod may influence prolactin secretion through a DA independent mechanism (as evidenced by the current study), and prolactin regulates the activity of hypothalamic DA pathways through a positive feedback mechanism. Evidence for the existence of such a feedback loop has been obtained in the ewe under both long and short days (26).…”