Function of Cathepsin K in the Central Nervous System of Male Mice is Independent of Its Role in the Thyroid Gland

Abstract

Function of cathepsin K in the central nervous system of male mice is independent of its role in the thyroid gland. Cellular and Molecular Neurobiology.

Cathepsin K: The Action in and Beyond Bone

“…Moreover, CatK-deficient mice exhibited reduced anxiety levels and both short-and long-term learning and memory deficits as compared to the wildtype mice (Dauth et al, 2011). Although two later studies by the same group have excluded the possible influence of CatK's function in thyroid and astrocytes on the brain phenotype of CatK-deficient mice (Dauth et al, 2012(Dauth et al, , 2019, the underlying molecular mechanism responsible for the CNS dysfunction in CatK-deficient mice remains elusive. Cumulatively, it indicates that the existence of CatK should be extremely vital for the development and metabolism of CNS.…”

Auto-Regulation of the Thyroid Gland Beyond Classical Pathways

“…Thyroid follicle area ↑ = a [22,26] ↑ a [63][64] = vy [65] ↑↑ vy [65] = y = a [25] Epithelial cell extensions ↓ = a [22,26] ↑ a [63][64] ↑ y ↑ a [25] Functional characteristics (Intrathyroidal status) TH generation Tg (mRNA, protein) ↑ ns a [22] = vy [24] = vy [65] ↑ vy [65] Tg multi-layers (IIF) = a [22] = y [24] = y [24] ↓ y [24] ↑ y = a [25] Tg multimers (PAGE) = a [22] ↑ vy ↓ y [24] = vy = y [24] ↓↓ vy ↓ y [24] = y ↓ a [25] Tg glycosylation (ConA + ve ) = y ↓↓ a [25] NIS (mRNA, protein) ↑ ns vy [65] = a [63] = vy [65] ↑↑ vy [65] TPO (mRNA, protein) = a [63] = vy [65] ↑↑ vy [65] Dehal1 (mRNA, protein) = a [63] = vy [65] Tshr (mRNA, protein) = a [63] = vy [65] ↑↑ vy [65] TH liberation Tg degradation states = a [22] = vy ↑ y [24] = vy = y [24] ↑ vy ↑ y [24] = y = a [25] Cath B protei...…”

“…Serum TT 4 = a [22,26] ↓ vy [65] = vy [65] = vy [65] = y = a [25] Serum TT 3 = a [22,26] ↑↑↑ vy [65] = vy [65] ↑↑↑ vy [65] = y = a [25] Serum TSH = a [22,26] ↑ a [65] = a [65] ↑ a [65] ↑↑ y = a [25] No change in comparison to wild type is depicted as = , a mild, moderate, and pronounced increase as ↑, ↑↑, and ↑↑↑, respectively, while a mild and moderate decrease is indicated as ↓ and ↓↓, respectively; non-significant trends are indicated as ns ; the animals age at the time of analysis is denoted as vy (very young), y (young), and a (adult) representing ages of < 2.5 months, 5-8 months, and 10-15 months, respectively ; "+ve" = "positive".…”

“…In the following, we will discuss recent insights into thyroid auto-regulation, which we chose to define as the ability of thyrocytes to maintain regular functional activities throughout all life stages, but focusing on the adult state. Important conclusions can be drawn when thyroid functionality is challenged, e. g., by knockingout thyroid function-critical genes [22][23][24][25][26] or by specifically inducing thyroid dysfunction in animal models [27][28][29][30][31]. Knowledge on the complexity of molecules and pathways involved in thyroid auto-regulation is continuously growing as their intricate interconnections are displayed in such animal models by the many mild and more severe phenotypes in thyroid functionality (▶table 1).…”

The Amino Acid Transporter Mct10/Tat1 Is Important to Maintain the TSH Receptor at Its Canonical Basolateral Localization and Assures Regular Turnover of Thyroid Follicle Cells in Male Mice

“…However, a role of Gα q -mediated TSH receptor signaling in hyperplasia-resulting thyrocyte proliferation cannot be ruled out [ 12 ]. On the contrary, genotypes featuring upregulation of Mct8 such as that observed in Ctsk −/− mice [ 8 ] result neither in altered thyroid functional nor morphological phenotypes [ 13 , 14 ]. Although it is known that serum TSH concentrations remain unaffected in Ctsk −/− mice [ 14 ] and are significantly [ 10 ] or moderately elevated in Mct8 deficiency [ 11 , 15 , 16 ] in young or adult mice, respectively, no information is available on the outcomes of TSH receptor signaling in genotypes where Mct8 is lacking (i.e., Mct8 −/y ) or upregulated (i.e., Ctsk −/− ).…”