The hatching process in the chicken is accompanied by dramatic changes in plasma thyroid hormones. The cause of these changes, though crucial for hatching and the onset of endothermy, is not known. One hypothesis is that the pituitary gland becomes more sensitive to hypothalamic stimulation during this period. We have tested whether the responsiveness of the thyrotropes to hypothalamic stimuli changes throughout the last week of embryonic development and hatching by studying the mRNA expression of receptors involved in the control of the secretory activity of this cell type. We used a real-time PCR set-up to quantify whole pituitary mRNA expression of the β subunit of thyrotrophin (TSH-β), type 1 thyrotrophin-releasing hormone receptor (TRH-R1), corticotrophin-releasing hormone receptors (CRH-R1 and CRH-R2) and somatostatin subtype receptor 2 (SSTR2) on every day of the last week of embryonic development, including the day of hatch and the first day of posthatch life. The thyrotrope-specific expression was investigated by a combination of in situ hybridization with immunohistochemistry at selected ages. Although TSH-β mRNA levels increased towards day 19 of incubation (E19), the expression of CRH-R2 and TRH-R1 mRNA by the thyrotropes tended to decrease during this period, suggesting a lower sensitivity of the thyrotropes to the stimulatory factors CRH and TRH. CRH-R1, which is not involved in the control of TSH secretion, increased steadily throughout the period tested. The expression of SSTR2 mRNA by the thyrotropes was low during embryonic development and increased just before hatching. We have concluded that the sensitivity of the pituitary thyrotropes to hypothalamic stimulation decreases throughout the last week of embryonic development, so that the higher expression of TSH-β mRNA around E16–E19, and hence the increasing plasma thyroxine level, is unlikely to be the result of an increased stimulation by either TRH or CRH.

In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor β2 (TRβ2) expression at the different levels of the hypothalamo–pituitary–thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRβ2 mRNA in retina, pineal gland, and the major control levels of the HPT axis – brain, pituitary, and thyroid gland – at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRβ2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRβ2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRβ2 mRNA throughout the diencephalon and confirmed the elevation in TRβ2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRβ2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRβ2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRβ2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRβ2 mRNA expression.

Pleomorphic adenoma gene 1 (PLAG1) belongs to the PLAG family of zinc finger transcription factors along with PLAG-like 1 and PLAG-like 2. The PLAG1 gene is best known as an oncogene associated with certain types of cancer, most notably pleomorphic adenomas of the salivary gland. While the mechanisms of PLAG1-induced tumorigenesis are reasonably well understood, the role of PLAG1 in normal physiology is less clear. It is known that PLAG1 is involved in cell proliferation by directly regulating a wide array of target genes, including a number of growth factors such as insulin-like growth factor 2. This is likely to be a central mode of action for PLAG1 both in embryonic development and in cancer. The phenotype of Plag1 knockout mice suggests an important role for PLAG1 also in postnatal growth and reproduction, as PLAG1 deficiency causes growth retardation and reduced fertility. A role for PLAG1 in growth and reproduction is further corroborated by genome-wide association studies in humans and domestic animals in which polymorphisms in the PLAG1 genomic region are associated with body growth and reproductive traits. Here we review the current evidence for PLAG1 as a regulator of growth and fertility and discuss possible endocrine mechanisms involved.