Phorbol esters have a dual action through protein kinase C in regulation of proliferation of FRTL-5 cells

AbstractIn quiescent rat thyroid (FRTL-5) cells, phorbol-12-myristate-13-acetate (PMA) inhibited DNA synthesis induced by a combination of insulin and thyrotropin (TSH) or dibutyryl cyclic AMP (Bt2cAMP). This inhibitory effect of PMA was observed even when PMA was added after addition of these growth factors, and was maximal when PMA was added 2–4 h after the growth factors (late in the G1-phase of the cell cycle). On the other hand, PMA alone induced DNA synthesis and also enhanced that induced by Bt2cAMP or insulin in these quiescent cells. 1-Oleoyl-2-acetylglycerol mimicked these effects of PMA, but 4α-phorbol-12,13-didecanoate had no effect. These data demonstrate that in FRTL-5 cells protein kinase C has a stimulatory effect on the G0 to G1 transition and an inhibitory effect on the G1 to S transition in the cell cycle

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society\u27s Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented

Functional regulation of GTP-binding protein coupled to insulin-like growth factor-I receptor by lithium during G1 phase of the rat thyroid cell cycle

AbstractThe regulatory effects of lithium on the function of pertussis toxin-sensitive GTP-binding (Gi)-proteins located on the mitogenic pathway activated by insulin-like growth factor-I (IGF-I) in FRTL-5 cells were studied. Addition of GTP-γ-S to the thyroid stimulating hormone-primed cell membranes resulted in a decreased affinity of IGF-I receptor binding, and the dissociation constant (Kd) increased from 0.46 nM to 3.1 nM. Moreover, IGF-I stimulated GTP-γ-S binding to a 40-kDa protein, and pertussis toxin (PT) attenuated the stimulatory effect of IGF-I on the same protein. Lithium lowered the affinity of IGF-I receptor binding and the Kd (3.4 nM) was in the same range as that in the presence of GTP-γ-S. The inhibitory effect of lithium was markedly abolished by pretreatment with PT. Lithium attenuated the amounts of ADP-rebosylation of the 40-kDa protein by PT. In addition, lithium stimulated Ca2+ entry, similar to that by IGF-I, and induced cell proliferation via a PT-sensitive step. These findings suggest that lithium may be capable of modulating the function of Gi-proteins coupled to IGF-I receptors during the G1 phase of the FRTL-5 cell cycle

A Patient with Primary Hyperparathyroidism Associated with Familial Hypocalciuric Hypercalcemia Induced by a Novel Germline CaSR Gene Mutation

We report a patient with familial hypocalciuric hypercalcemia (FHH) associated with primary hyper-parathyroidism (PHPT) and incidental papillary thyroid carcinoma. The patient showed hypercalcemia, high parathyroid hormone (PTH) levels and low urinary calcium excretion. A computed tomography (CT) scan revealed an enlarged parathyroid gland. Ultrasonography (US) and aspiration cytology revealed microcarcinoma of the left lobe of the thyroid gland. Screening studies of his family revealed that four of five family members had hypocalciuric hypercalcemia and normal PTH level. Sequencing analysis of the calcium sensing receptor gene revealed a novel heterozygous mutation (3193delA) in the patient and his family members with hypercalcemia, but one with normocalcemia. The patient underwent total thyroidectomy, central node dissection and extirpation of the enlarged parathyroid gland. Surgery is not indicated for FHH; however, FHH may be accompanied with parathyroid adenoma causing PHPT, as reported here, for which surgical treatment is indicated