In order to determine the role of the pineal gland in mediating the effects of long-term light deprivation on prolactin (PRL) cell activity in a highly photosensitive species, PRL synthesis, storage and release were determined in both female and male Syrian hamsters that were either blind, blind and pinealectomized or left intact for 14 weeks. PRL release was determined in vivo by measuring the amount of immunoreactive (RIA) PRL in the serum of the animals in each group with a heterologous RIA for hamster PRL. Blinding resulted in a 98 and 88% reduction in serum PRL levels in female and male hamsters, respectively. Pinealectomy largely prevented the suppressive effects of blinding on PRL release; however, PRL levels in blind pinealectomized animals were intermediate between those in intact and blind animals. PRL synthesis was evaluated by assessing the amount of ³H-leucine incorporated into PRL by anterior pituitaries in vitro. In female hamsters 14 weeks of light deprivation resulted in an 87% decrease in the incorporation of ³H-leucine into newly synthesized PRL whereas in males only a 40% reduction occurred. While pinealectomy completely prevented the inhibitory effects of blinding on PRL synthesis in males, it was less effective in female hamsters inasmuch as PRL synthesis was still nearly 50% lower in blind pinealectomized animals than in controls. Stored PRL, as represented by the total amount of RIA-PRL in vitro, was 96% lower in blind female hamsters as compared with intact controls; in blind male hamsters, stored PRL was reduced by 77%. As in the case of PRL synthesis, pinealectomy completely prevented the suppressive effects of blinding on PRL storage in males; however, it was only partially effective in female animals since total RIA-PRL was still 58% less than in controls. In conclusion, it appears that the inhibitory effects of light deprivation on PRL cell activity are more severe in female than in male hamsters. Furthermore, while the suppressive effects of blinding on PRL cell function in males seem to be pineal-dependent, they appear to be at least partially pineal-independent in female animals.

Summary Melatonin (aMT) appears to be a potentially important oncostatic substance that can block the mitogenic effects of tumour-promoting hormones and growth factors such as oestradiol and epidermal growth factor, in vitro. In the present study, we examined the possibility that aMT would also inhibit the stimulatory effects of the tumour-promoter prolactin (PRL) on MCF-7 and ZR75-1 human breast cancer cell (HBC) growth under 5% charcoal-stripped fetal bovine serum culture conditions. Human PRL (10-100ng ml-') stimulated the rate of MCF-7 and ZR-75-1 HBC growth up to 2-fold above that of untreated controls. Melatonin, at concentrations between 1012-M and 10-5M, diminished and at physiological levels completely abolished PRL's mitogenic activity, but had no effect on growth in the absence of PRL. The mitogenic effects of human growth hormone (hGH), a PRL-related hormone, and also of several monoclonal antibodies (MAbs) against the PRL receptor (PRLR), were also abrogated by physiological concentrations of aMT. Additionally, aMT blocked the enhancement of MAb mitogenic activity induced by a second 'cross-linking' antibody (CLA). These findings indicate that aMT interrupts the PRLR-mediated growth signal in HBC and suggest that the oncostatic activity of aMT may also be linked with an antagonism of PRL's actions.

The purpose of this investigation was to elucidate the differences in the nature and time course of changes in in vitro prolactin (PRL) cell activity between blinded and blind/pinealectomized female hamsters. Adult female golden hamsters were either left intact, blinded and sham-pinealectomized (Blind/Sham) or blinded and pinealectomized (Blind/ Pinx). Twelve weeks after surgeries, animals were killed by decapitation and randomized hempituitaries were incubated for a total of either 30, 60, 90, 120, 180 or 240 min. PRL release in vivo, as estimated by monitoring serum titers of immunoreactive PRL (IR-PRL), was markedly reduced in Blind/Sham animals; pinealectomy completely prevented this depression. PRL storage was assessed by measuring total levels (i.e., medium + pituitaries) of IR-PRL in vitro. Total, pituitary and media values of IR-PRL were all significantly depressed in Blind/Sham females. Pinealectomy of blinded animals almost completely prevented these reductions. PRL synthesis, as evaluated by measuring the amount of ³H-leucine incorporated into PRL in vitro, was profoundly reduced in Blind/Sham females. Surprisingly, pinealectomy failed to prevent the blinding-induced decrease in PRL production. From these data, we conclude that in the light-deprived female hamster the pineal gland inhibits PRL storage and release, while the depression in PRL synthesis may be independent of a pineal influence.

Since the exact nature of the hypothalamic regulation of prolactin (PRL) cell activity in the photosensitive female Syrian hamster is unknown, the present investigation was designed to determine whether dopamine (DA), a physiological PRL-inhibitory hormone in the rat, inhibits the synthesis and release of female hamster PRL in vitro via a DA receptor-mediated mechanism. Anterior pituitary glands from long photoperiod-exposed adult female Syrian hamsters were incubated in the presence of increasing concentrations of DA (5 nM, 500nM and 50 microM) in Kreb's Ringer Bicarbonate medium for 2 hours following a preincubation period of 1 hour in medium not containing DA. While PRL synthesis, as measured by the incorporation of 3H-leucine into PRL, was unaffected by DA, the release of immunoreactive (RIA)-PRL into the medium was inhibited by 55% and 53% by 500 nM and 50 microM DA, respectively; however, these same concentrations of DA inhibited the release of 3H-PRL into the medium by only 25% and 23%, respectively. The DA receptor blocker, pimozide (PIM) was effective in blocking the PRL-inhibitory effects of DA (500 nM) on both RIA- and 3H-PRL release in vitro. These are the first data suggesting that DA directly inhibits PRL release from female hamster anterior pituitary glands via a DA receptor-mediated mechanism.