Suckling reverses mammotrope responsiveness to TRH.
It is well established that suckling can alter the responsiveness of mammotropes to the prolactin (PRL) releasing actions of thyrotropin-releasing hormone (TRH). The purpose of the present study was to more critically characterize this phenomenon and to determine whether this effect was manifested at the point of TRH receptor binding and effector coupling. Cultured anterior pituitary (AP) cells from suckled and nonsuckled rats were subjected to reverse hemolytic plaque assays for PRL in the absence or presence of TRH. Treatment with TRH (100 nM for 2 h) significantly stimulated PRL secretion by pituitary cells from transiently suckled females (to 147.0 +/- 0.7% of control value; P < 0.05). Surprisingly, this same dose of the secretagogue caused a 30% inhibition (P < 0.05) of PRL release by AP cells obtained from nonsuckled lactators. In order to gain some insight into the possible mechanisms that govern these drastic changes in mammotrope responsiveness to TRH, we evaluated the ability of this secretagogue to activate the phosphoinositidase pathway. To this end, we chose to measure the intracellular accumulation of inositol monophosphate (IP1), a degradative metabolite of the inositol 1,4,5-triphosphate (Ins 1,4,5-P3) second messenger molecule, in the presence of LiCl (10 mM) which prevents further metabolism of IP1. We found that a 2 h exposure to 100 nM TRH resulted in a 3-fold increase in IP1 accumulation by AP cultures derived from both suckled and nonsuckled dams. Our results indicate that TRH effectively activates its receptor and couples to the phosphoinositidase pathway in AP cells from both nonsuckled and suckled females. Thus, we conclude that the suckling-induced increase in mammotrope responsiveness to TRH is regulated subsequent to TRH receptor activation.
Hill
J B
JB
Department of Anatomy and Cell Biology, Medical University of South Carolina, Charleston 29425.
Ramsdell
J S
JS
Frawley
L S
LS
D000818:Animals; D000833:Animals, Suckling / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin