Has the mammary gland a protective mechanism against overexposure to triiodothyronine during the peripartum period? The prolactin pulse down-regulates mammary type I deiodinase responsiveness to norepinephrine.
Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure.
Anguiano
B
B
Instituto de Neurobiología, UNAM-Juriquilla, Querétaro, México 76230.
Rojas-Huidobro
R
R
Delgado
G
G
Aceves
C
C
D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D007453:Iodide Peroxidase / Q000378:metabolism; D007743:Labor, Obstetric / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*
D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D019938:Cyclin D1; D011388:Prolactin; D007453:Iodide Peroxidase; D009638:Norepinephrine