Mammary Gland Sympathetic Innervation Is a Major Component in Type 1 Deiodinase Regulation

Abstract

Recent observations have shown that in lactating rats previously deprived of suckling, either suckling stimulus or ip injection of norepinephrine was capable of increasing mammary deiodinase type 1 (M-D1) mRNA content and enzyme activity. In the present work, we show that intact efferent sympathetic mammary innervation is required to restore both mammary D1 mRNA content and enzyme activity, whereas suckling-induced secretion of catecholamines from the adrenal glands does not seem to participate in M-D1 enzyme regulation. The data also indicate that the sympathetic reflex activation in response to suckling involves two complementary autonomic components: (1) activation, presumably through mammary segmental arrangement affecting neighboring mammary glands; and (2) an individual reflex regulatory mechanism capable of maintaining M-D1 activity within each mammary gland. In addition to these findings, we show that the suckling-induced sympathetic activation of M-D1 activity could be blocked by prior activation of ductal mechanoreceptors. This set of regulatory and counterregulatory mechanisms seems to ensure the optimal control of mammary energetic expenditure according to litter size.

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

“…We have previously demonstrated that suckling is essential to maintain MDio1 levels during lactation and that adrenergic innervation is the direct activator (Aceves et al 1999b). In the present work we used the same approach to analyze the regulation of MDio1 and other thyroid components during the pregnancy and peripartum periods.…”

Effect of suckling and adrenergic stimulation on peripheral deiodination in lactating rats: differential expression of type 1 deiodinase mRNA forms

“…This notion agrees with previous observations showing that (1) the characteristic homeorhetic adjustments of lactation are modulated by the lactational intensity (litter size, number and frequency of suckling, etc.) (Prentice & Prentice 1988, Valverde-R & Aceves 1989; (2) mammary D1 is stimulated in vivo by the NE released in the sympathetic nerve endings (Aceves et al 1999b);and (3) in the heart, a classic noradrenergic target tissue, lactation increases the NE turnover rate (Bauman & Currie 1980).…”

“…Extensive clinical and experimental data indicate that the reciprocal functional relationship between the thyroid and the sympathetic nervous system (SNS) constitutes a critical part of the homeorhetic mechanisms aimed at preserving the organism's metabolic fitness (Aceves et al 1994, Silva 1996. Lactation is an excellent example of these homeorhetic adjustments and, in terms of peripheral thyronine deiodination, we have shown that (1) despite the hyperphagia present during lactation, the organ-specific adjustments in peripheral deiodination resemble those observed in fasted or hypothyroid animals (Valverde-R & Aceves 1989, Aceves et al 1994; (2) these adjustments are not modified by overfeeding or by thyroid hormone administration (Aceves et al 1994); (3) this 'pseudohypothyroidism' is exacerbated when the lactational demand (litter size) is increased (Valverde-R & Aceves 1989); (4) D1 enzyme is encoded by two messengers that differ in the length of their 3 -untranslated region (3 UTR), and the expression of the large form is directly correlated to thyroid status (Navarro et al 1997); (5) MG D1, which is encoded by the short messenger, is positively regulated by suckling through the efferent sympathetic mammary innervation (Aceves et al 1999a);and (6) this local MG D1 regulation involves segmental mechanisms that, depending on the size of the litter, may allow a differential, gland by gland adjustment of energetic expenditure (Aceves et al 1999b). These findings add further support to our proposal that, during lactation, deiodination represents a functional intersection of the dyad thyroid-SNS to maintain the elevated energy supply needed by the lactating mammary gland (Aceves et al 1999b).…”

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences

“…Identification of the SECIS element in the D1 3' UTR recognized D1 as only the second eukaryotic mRNA encoding a selenoprotein [27]. Rat D1 is encoded by at least two different transcripts that vary in length at the 3' UTR, but their significance, if any, has not been clarified [38,39]. Two single nucleotide polymorphisms (SNPs) were identified in the 3' UTR of the human D1 mRNA, D1a-C/T at position 785 and D1b-A/G at position 1814, the latter being 33 nucleotides 3' to the SECIS element [40].…”