16 research outputs found
Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut
Fish larval development, not least the spectacular
process of flatfish metamorphosis, appears to be
under complex endocrine control, many aspects of
which are still not fully elucidated. In order to obtain
data on the functional development of two major
endocrine glands, the pituitary and the thyroid, during
flatfish metamorphosis, histology, immunohistochemistry
and in situ hybridization techniques were applied on
larvae of the Atlantic halibut (Hippoglossus hippoglossus),
a large, marine flatfish species, from hatching
through metamorphosis. The material was obtained
from a commercial hatchery. Larval age is defined as
day-degrees (D =accumulated daily temperature from
hatching). Sporadic thyroid follicles are first detected in
larvae at 142 D (27 days post-hatch), prior to the
completion of yolk sack absorption. Both the number
and activity of the follicles increase markedly after yolk
sack absorption and continue to do so during subsequent
development. The larval triiodothyronine (T3)
and thyroxine (T4) content increases, subsequent to yolk
absorption, and coincides with the proliferation of thyroid
follicles. A second increase of both T3 and T4 occurs
around the start of metamorphosis and the T3 content
further increases at the metamorphic climax. Overall,
the T3 content is lower than T4. The pituitary gland can
first be distinguished as a separate organ at the yolk sack
stage. During subsequent development, the gland becomes
more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia
(PI). The first sporadic endocrine pituitary cells are observed
at the yolk sack stage, somatotrophs (growth
hormone producing cells) and somatolactotrophs (somatolactin
producing cells) are first observed at 121 D
(23 days post-hatch), and lactotrophs (prolactin producing
cells) at 134 D (25 days post-hatch). Scarce
thyrotrophs are evident after detection of the first thyroid
follicles (142 D ), but coincident with a phase in
which follicle number and activity increase (260 D ).
The somatotrophs are clustered in the medium ventral
region of the PD, lactotrophs in the anterior part of the
PD and somatolactotrophs are scattered in the mid and
posterior region of the pituitary. At around 600 D ,
coinciding with the start of metamorphosis, somatolactotrophs
are restricted to the interdigitating tissue of the
NH. During larval development, the pituitary endocrine
cells become more numerous. The present data on thyroid
development support the notion that thyroid hormones
may play a significant role in Atlantic halibut
metamorphosis. The time of appearance and the subsequent
proliferation of pituitary somatotrophs, lactotrophs,
somatolactotrophs and thyrotrophs indicate at
which stages of larval development and metamorphosis
these endocrine cells may start to play active regulatory
roles.This work has been carried out within the
projects ‘‘Endocrine Control as a Determinant of Larval Quality in
Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The
Molecular and Endocrine Basis of Flatfish Metamorphosis’’
(Q5RS-2002-01192), with financial support from the Commission
of the European Communities. However, it does not necessarily
reflect the Commission’s views and in no way anticipates its future
policy in this area. This project was further supported by the
Swedish Council for Agricultural and Forestry Research and Pluriannual
funding to CCMAR by the Portuguese Science and
Technology Council
Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?
Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically
important as predators, prey and structure-builders. Bioregulatory molecules (e.g.,
amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling
pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used
in toxicity testing, but few studies have used cnidarians in explicit testing for signal
disruption. Sublethal endpoints developed in cnidarians include budding, regeneration,
gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic
databases, microarrays and other molecular tools are increasingly facilitating mechanistic
investigation of signaling pathways and signal disruption. Elucidation of cnidarian
signaling processes in a comparative context can provide insight into the evolution and
diversification of metazoan bioregulation. Characterizing signaling and signal disruption
in cnidarians may also provide unique opportunities for evaluating risk to valuable
marine resources, such as coral reefs
Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)
Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections
How does fish metamorphosis affect aromatic amino acid metabolism?
Aromatic amino acids (AAs, phenylalanine and tyrosine) may be specifically required during fish metamorphosis, since they are the precursors of thyroid hormones which regulate this process. This project attempted to evaluate aromatic AA metabolism during the ontogenesis of fish species with a marked (Senegalese sole; Solea senegalensis) and a less accentuated metamorphosis (gilthead seabream; Sparus aurata). Fish were tube-fed with three l-[U-14C] AA solutions at pre-metamorphic, metamorphic and post-metamorphic stages of development: controlled AA mixture (Mix), phenylalanine (Phe) and tyrosine (Tyr). Results showed a preferential aromatic AA retention during the metamorphosis of Senegalese sole, rather than in gilthead seabream. Senegalese sole’s highly accentuated metamorphosis seems to increase aromatic AA physiological requirements, possibly for thyroid hormone production. Thus, Senegalese sole seems to be especially susceptible to dietary aromatic AA deficiencies during the metamorphosis period, and these findings may be important for physiologists, fish nutritionists and the flatfish aquaculture industry
Involvement of growth hormone-insulin-like growth factor I
The role of growth hormone (GH) and insulinlike growth factor-I (IGF-I) in the tissue remodeling associated with the transition of a symmetrical larva to an
asymmetrical juvenile during flatfish metamorphosis is unknown. In order to investigate the potential role of these
hormones in the remodeling of cranial bone and soft tissue that accompanies eye migration during metamorphosis of Atlantic halibut (Hippoglossus hippoglossus) larvae, tissuespecific gene expression was monitored by in situ hybridization for Atlantic halibut type I growth hormone receptor
(hhGHR), type II hhGHR, and insulin-like growth factor-I receptor (hhIGF-IR). Polyclonal antibody generated against
the extracellular domain of type I hhGHR was used for the immunohistochemical localization of type I GHR protein. Type I hhGHR, type II hhGHR, and hhIGF-IR mRNA were
expressed in fibroblasts, frontal bone osteocytes, and dorsal chondrocytes at the onset of metamorphosis (stage 8),during metamorphic climax (stage 9), and in fully metamorphosed juveniles (stage 10). Type I GHR protein showed similar expression patterns to those of type I hhGHR mRNA, except in chondrocytes in which little
GHR protein was detected. The localization of GHR and IGF-IR transcripts and GHR protein in cranial structures that undergo remodeling is intriguing and suggests that, in addition to thyroid hormones, the GH-IGF-I system is involved in morphological transformations during metamorphosis
in Atlantic halibut.We thank Heiddis Smáradóttir, Arnar Jónsson,
and Øystein Saele for larval sampling, and Nádia Silva for methodological assistance