Reversal by thiols of dopamine-, stalk-median eminence-, and zinc-induced inhibition of prolactin transformation in adenohypophyses of lactating rats.

Depletion-transformation of PRL is a decrease in tissue PRL detectability which precedes and may often be required for increased PRL release. The present studies were designed to determine whether thiol-disulfide interchange mechanisms may be involved in PRL transformation and release by the pituitary of the lactating rat. Thirds of 8-h nonsuckled lactating rat adenohypophyses were incubated with or without thiols (reduced glutathione, the aminothiol cysteamine, or mercaptoethanol), in the presence of known inhibitors of transformation and release such as dopamine (DA), stalk median eminence (SME) extract, or Zn++. PRL concentrations in pre- and postincubated tissues, as well as the amount of released PRL, were determined by polyacrylamide gel electrophoresis and densitometry. In 30-min incubations without additions, 12-22% of the tissue PRL was depleted; however, in the presence of 17-50 microM DA, all doses of SME extracts tested (0.5-2.0 eq), or 0.1 mM Zn++, depletion was partially or totally prevented and PRL release was inhibited 25-60%. On the other hand, when thiols were added in addition to the above agents, a complete, dose-related, restoration of PRL depletion was obtained. In 120-min incubations, thiols similarly reversed the effects of 0.05 mM DA on depletion, but thiols did not reverse the inhibition of PRL release caused by DA, SME, or Zn++. Other data indicate that thiols alone may inhibit rat PRL release and also facilitate or induce PRL depletion; in bovine PRL granules, thiols reverse Zn++ inhibition of PRL release and detectability. These data suggest that thiol-disulfide interchange reactions may be importantly involved in both depletion-transformation and in secretion. The precise thiol sensitivity of the two processes does not appear identical, secretion being more sensitive to DA and less sensitive to thiols than depletion-transformation.