Mammary Type I Deiodinase Is Dependent on the Suckling Stimulus: Differential Role of Norepinephrine and Prolactin*

Abstract

Mammary deiodinase type I (M-D1) is present only during lactation and exhibits a clear direct correlation with lactation intensity (size of litters). The present work shows that M-D1 is suckling dependent and that intervals between suckling periods no longer than 12 h are essential to maintain this activity. Moreover, we find that with only 15 min of resuckling in 12-h nonsuckled mothers, the 50% decrease in both M-D1 messenger RNA and enzymatic activity could be restored to control values. This restorative effect by suckling may involve pre- and posttranscriptional mechanisms in which norepinephrine and PRL play important roles. Norepinephrine elicits a potent stimulatory effect on M-D1 messenger RNA and enzyme activities, whereas PRL only increases M-D 1 activity and may modulate the enzyme response to norepinephrine. Oxytocin and GH had no effect. These data suggest that the adrenergic nervous system and PRL could directly participate in mammary energetic expenditure, regulating the local T3 supply.

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].…”

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

“…D1 or D2 mRNAs were identified by using a previously standardized semi-quantitative PCR procedure in which an amplicon of the structural protein cyclophilin (Cyc) was simultaneously amplified (Aceves et al 1999a). Briefly, the reverse transcription (RT) reaction was primed with oligo(dT) and subscripted with 5 µg total RNA.…”

“…The length of 3 UTR D1 mRNA was assessed by using a previously standardized 3 -rapid amplification cDNA ends (RACE) procedure (Aceves et al 1999a) and 5 µg total RNA from liver, heart and MG. The RT reaction was primed with oligo(dT) containing a terminal specific sequence, AP (see Fig.…”

“…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).…”

Human Breast Cancer Tissue Expresses High Level of Type 1 5′-Deiodinase

“…In humans, D1 is present mainly in the liver, kidneys, thyroid, and pituitary gland, while D2 is chiefly expressed in the central nervous system, pituitary gland, skeletal muscle, and thyroid (2). There is no data available on D1 expression in healthy human breast tissue or human breast cancer tissue, although a few reports have documented the presence of D1 activity in rat mammary glands or breast cancer in rats (3)(4)(5)(6)(7). To the contrary, decreased D1 activity has been observed in other cancers, such as renal clear cell carcinoma (8), papillary thyroid cancer tissue (9) as well as papillary (10) and follicular (11) thyroid cancer cell lines, lung cancer (12), and in some pituitary tumors (13) when compared to their healthy counterparts.…”