Triiodothyronine expands the lactotroph and maintains the lactosomatotroph population, whereas thyrotrophin-releasing hormone augments thyrotroph abundance in aggregate cell cultures of postnatal rat pituitary gland

In the present study, we used a three-dimensional pituitary cell culture system from early postnatal rats to examine the in vitro developmental potential of triiodothyronine (T3) and thyrotrophin-releasing hormone (TRH). Cell types were identified at the hormone mRNA level by single-cell reverse transcription-polymerase chain reaction and any change in abundance was further examined by immunofluorescence staining of the corresponding hormone protein. In aggregates from 14-day-old rats, long-term (12-16 days) treatment with T3 (0.5 nM) increased the abundance of cells expressing prolactin mRNA (PRLmRNA cells) by 2.5-fold and lowered that of nonhormonal cells and thyroid-stimulating hormone beta (TSHbeta)mRNA cells. The abundance of growth hormone (GH)mRNA cells decreased during culture compared to that in the freshly dispersed pituitary gland and T3 did not significantly affect this cell population. Cells coexpressing PRL mRNA and GH mRNA virtually disappeared during culture but reappeared in the presence of T3. T3 increased the abundance of PRL-immunoreactive (ir) cells in aggregates from 14-day-old rats, as well as in aggregates from newborn and 1-week-old rats. As estimated by bromodeoxyuridine (BrdU) labelling, a 3-day treatment with T3 enhanced the number of PRL-ir cells that had incorporated BrdU, but did not yet expand the total population of PRL-ir cells. Long-term treatment with TRH (100 nM) did not affect the proportion of PRLmRNA or GHmRNA cells, but consistently increased the proportional number of TSHbeta(mRNA) and TSHbeta-ir cells. The present data confirm the findings obtained in recent in vivo loss of function genetic studies suggesting that T3 plays a prominent role in postnatal expansion of the lactotroph population and that TRH is important for thyrotroph development. The data suggest that the effect of T3 is brought about by a direct action on the pituitary gland through a cell proliferation mechanism. T3 also appears to support the lactosomatotroph population. In view of the established theory that lactotrophs develop from GH-expressing progenitor cells and that this is a post mitotic event, we propose that T3 is mitogenic for GHmRNA cells that lack GH-ir material and that transdifferentiate into PRL-ir cells, but that a pathway of PRL cell development from mitotic nonhormonal cell progenitors may also be involved.status: publishe

A Pituitary cell type coexpressing messenger ribonucleic acid of proopiomelanocortin and the glycoprotein hormone alpha-subunit in neonatal rat and chicken: rapid decline with age and reappearance in vitro under regulatory pressure of corticotropin-releasing hormone in the rat

Promiscuous hormone mRNA expression in the pituitary remains poorly understood. We examined by means of RT-PCR and immunostaining whether glycoprotein hormone alpha-subunit (alphaGSU) could be coexpressed with proopiomelanocortin (POMC) in vivo and under pressure of CRH in vitro. Cells coexpressing alphaGSU and POMC mRNA amounted to 2.6% of the cells in ex vivo rat pituitary at birth [postnatal d 1 (P1)], fell to much lower level at P14, and were undetectable in adulthood. In cultured pituitary aggregates of P14 rats, alphaGSU/POMC cells remained scarce but represented up to 6.6% after chronic treatment with CRH but not leukemia inhibitory factor. CRH was less effective in aggregates from P1 and adult rats. The total alphaGSU population ex vivo at P1 was two times smaller than at P14, but in culture it expanded 2.5 times, concomitantly with a reciprocal change in POMC cell abundance. Tpit transcripts were detected in POMC-only and alphaGSU/POMC cells but not in alphaGSU-only cells. Cells coexpressing alphaGSU and POMC mRNA were relatively abundant in P14 chicken pituitary and aggregate cultures, but occurrence was not affected by CRH. Immunostaining showed alphaGSU and POMC colocalization in sporadic cells in intact rat pituitary and CRH-treated cultures at P1 but not at P14 and adult age. The data demonstrate the occurrence of cells coexpressing alphaGSU and POMC in rat and chicken pituitary. The developmental dynamics of this cell population and its response to CRH in vitro in the rat suggest a relationship of these cells with the embryonic branching of the POMC and alphaGSU cell lineages and their mutually opposite developmental course during early postnatal life.status: publishe

Combinatorial expression of phenotypes of different cell lineages in the rat and mouse pituitary

As studied by single cell RT-PCR of pituitary hormones, we demonstrated that the pituitaries of rats and mice contain a subpopulation of cells that express two or more hormone phenotypes typically belonging to lineages that are branched separately early during embryonic development, such as glycoprotein hormone alpha-subunit (alphaGSU) mRNA + PRL mRNA, alphaGSU mRNA + POMC mRNA, and POMC mRNA + GH or PRL mRNA. GnRH in vitro selectively expands the population of cells coexpressing alphaGSU mRNA + PRL mRNA, and CRH selectively increases the proportion of cells coexpressing alphaGSU mRNA + POMC mRNA. Colocalization of alphaGSU + PRL or alphaGSU + POMC could not be detected by double immunofluorescence. This lineage promiscuity was also observed in the pituitary in vivo.status: publishe

COGNOS:Care for People With Cognitive Dysfunction A National Observational Study

<p>Care plans are intended to improve the independence and functioning of patients with cognitive dysfunction and support the caregivers involved. They are an integral part of the Belgian reimbursement procedure for cholinesterase inhibitors. This nationwide, multicenter, observational study examined the content and implementation of the care plan along with patient satisfaction in community-dwelling patients newly diagnosed with Alzheimer disease in Belgium. The patients' opinion of their quality of life was measured using Anamnestic Comparative Self-Assessment (ACSA) scale. A total of 720 participants (453 female) were enrolled with 86.0% (619/719) living at home alone or with their spouse/partner. Cognitive problems (627/717, 87.4%) were the main reason for initiation of the consultation. Most patients had a caregiver (646/719, 89.8%): generally the spouse/partner (351/646, 54.3%) or a child (232/646, 35.9%). A total of 511 patients (71.0%) were prescribed a cholinesterase inhibitor after the initial consultation. A total of 236 care plans were advised with 169 (71.6%) realized and 157 of these (92.9%) considered adequate. Most patients were satisfied with the help received in the care plan (service satisfaction range, 80.0% to 98.6% of patients). Quality of life as rated by the patient significantly increased between baseline (average ACSA score: 5.2 +/- 2.4) and follow-up (5.8 +/- 2.1). The use of care plans appears to improve management of care for Alzheimer disease patients.</p>

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to the m.14487T>C mutation in ND6

Mitochondrial disorders of the oxidative phosphorylation (OXPHOS) system effect ~1/5000 individuals in the general population and present with a surprisingly wide range of multisystemic and neuromuscular phenotypes. The m.14487T>C mutation is a known pathogenic mtDNA mutation resulting in an amino acid substitution (p.M63V) in NADH dehydrogenase 6 (MT ND), a complex I subunit of the mitochondrial respiratory chain. Thus far it has been found in isolated cases with infantile Leigh syndrome and progressive dystonia. We report here adult and late-onset phenotypes as it was seen in a 5-generation Belgian family with 12 affected family members. Clinical and mutation load data were available for 9 family members, while biochemical analysis of the respiratory chain was performed in 3 muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leukocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leukocytes, 100 % in muscle). We found lower mutation loads (8-35% in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensoneural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue of these patients. Conclusion: The m.14487T>C mutation resulted in a broad spectrum of phenotypes in our family. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect