Pituitary gland height evaluated with magnetic resonance imaging in premature twins: the impact of growth and sex.

BACKGROUND: Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. OBJECTIVE: To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. MATERIALS AND METHODS: A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. RESULTS: When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. CONCLUSION: After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth.

Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury.

Recently, we discovered that the cytokine interleukin-6 (IL-6) acts as a pituitary stem cell-activating factor, both when administered in vivo and when added to stem cell organoid cultures in vitro. Moreover, its expression, predominantly localized in the gland's stem and mesenchymal cells, promptly increases following damage in the adult pituitary, leading to stem-cell proliferative activation. Given these findings that IL-6 is involved in pituitary stem cell regulation, we addressed the question whether the cytokine has an impact on the pituitary phenotype during active phases of the gland's remodeling, in particular embryonic development and neonatal maturation, as well as during homeostasis at adulthood and aging, all unknown today. Using the IL-6 knock-out (KO) mouse model, we show that IL-6 is dispensable for pituitary embryonic and neonatal endocrine cell development, as well as for hormonal cell homeostasis in adult and aging glands. The findings match the absence of effects on the stem cell compartment at these stages. However, using this IL-6 KO model, we found that IL-6 is needed for the acute stem-cell proliferative activation reaction upon pituitary injury. Intriguingly, regeneration still occurs which may be due to compensatory behavior by other cytokines which are upregulated in the damaged IL-6 KO pituitary, although at lower but prolonged levels, which might lead to a delayed (and less forceful) stem cell response. Taken together, our study revealed that IL-6 is dispensable for normal pituitary development and homeostasis but plays a key role in the prompt stem cell activation upon local damage, although its presence is not essentially needed for the final regenerative realization.

Actions and Roles of FSH in Germinative Cells.

Follicle stimulating hormone (FSH) is produced by the pituitary gland in a coordinated hypothalamic-pituitary-gonadal (HPG) axis event, plays important roles in reproduction and germ cell development during different phases of reproductive development (fetal, neonatal, puberty, and adult life), and is consequently essential for fertility. FSH is a heterodimeric glycoprotein hormone of two dissociable subunits, α and ß. The FSH ß-subunit (FSHß) function starts upon coupling to its specific receptor: follicle-stimulating hormone receptor (FSHR). FSHRs are localized mainly on the surface of target cells on the testis and ovary (granulosa and Sertoli cells) and have recently been found in testicular stem cells and extra-gonadal tissue. Several reproduction disorders are associated with absent or low FSH secretion, with mutation of the FSH ß-subunit or the FSH receptor, and/or its signaling pathways. However, the influence of FSH on germ cells is still poorly understood; some studies have suggested that this hormone also plays a determinant role in the self-renewal of germinative cells and acts to increase undifferentiated spermatogonia proliferation. In addition, in vitro, together with other factors, it assists the process of differentiation of primordial germ cells (PGCLCs) into gametes (oocyte-like and SSCLCs). In this review, we describe relevant research on the influence of FSH on spermatogenesis and folliculogenesis, mainly in the germ cell of humans and other species. The possible roles of FSH in germ cell generation in vitro are also presented.

New insights into the role and origin of pituitary S100ß-positive cells.

In the anterior pituitary, S100ß protein (S100ß) has been assumed to be a marker of folliculo-stellate cells, which are one of the non-hormone-producing cells existing in the parenchyma of the adult anterior lobe and are composed of subpopulations with various functions. However, recent accumulating studies on S100ß-positive cells, including non-folliculo-stellate cells lining the marginal cell layer (MCL), have shown the novel aspect that most S100ß-positive cells in the MCL and parenchyma of the adult anterior lobe are positive for sex determining region Y-box 2 (SOX2), a marker of pituitary stem/progenitor cells. From the viewpoint of SOX2-positive cells, the majority of these cells in the MCL and in the parenchyma are positive for S100ß, suggesting that S100ß plays a role in the large population of stem/progenitor cells in the anterior lobe of the adult pituitary. Reportedly, S100ß/SOX2-double positive cells are able to differentiate into hormone-producing cells and various types of non-hormone-producing cells. Intriguingly, it has been demonstrated that extra-pituitary lineage cells invade the pituitary gland during prenatal pituitary organogenesis. Among them, two S100ß-positive populations have been identified: one is SOX2-positive population which invades at the late embryonic period through the pituitary stalk and another is a SOX2-negative population that invades at the middle embryonic period through Atwell's recess. These two populations are likely the substantive origin of S100ß-positive cells in the postnatal anterior pituitary, while S100ß-positive cells emerging from oral ectoderm-derived cells remain unclear.

Delayed Postnatal Growth and Anterior Pituitary Development in Growth-Retarded (grt) Female Mice.

Growth-retarded (grt) mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined somatic growth, anterior pituitary development, and hormonal profiles in female grt mice and normal ones. Although growth in grt females was suppressed 2 weeks after birth, the measured growth parameters and organ weights gradually increased and finally reached close to the normal levels. Grt mice exhibited delayed eye and vaginal openings and remained in a state of persistent diestrus thereafter, plasma estrogen levels being lower than those in normal mice. Grt mice that received normal-donor thyroids showed accelerated growth and their body weights increased up to the sham-normal levels, indicating the importance of early thyroid hormone supplementation. In the anterior pituitary, there were fewer growth hormone (GH) and prolactin (PRL) cells in grt mice than in normal mice as examined at 12 weeks after birth, but the numbers of these cells did not differ from those in normal mice after 24 weeks. Grt mice had more TSH cells than normal mice until 48 weeks. Plasma GH levels in grt mice were lower than those in normal mice at 2 weeks, but did not differ substantially after 5 weeks. Compared with normal mice, grt mice had significantly lower plasma PRL and thyroxine levels, but notably higher TSH levels until 48 weeks. These findings indicate that thyroid hormone deficiency in grt mice causes delayed development and growth, and inappropriate development of GH, PRL and TSH cells, followed by the abnormal secretion of hormones by these pituitary cells.

Dynamic Expression of Imprinted Genes in the Developing and Postnatal Pituitary Gland.

In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting disorders (IDs) are caused by genetic and epigenetic mechanisms that alter the expression dosage of imprinted genes. Due to improvements in diagnosis, increasing numbers of patients with IDs are now identified and monitored across their lifetimes. Seminal work has revealed that IDs have a strong endocrine component, yet the contribution of imprinted gene products in the development and function of the hypothalamo-pituitary axis are not well defined. Postnatal endocrine processes are dependent upon the production of hormones from the pituitary gland. While the actions of a few imprinted genes in pituitary development and function have been described, to date there has been no attempt to link the expression of these genes as a class to the formation and function of this essential organ. This is important because IDs show considerable overlap, and imprinted genes are known to define a transcriptional network related to organ growth. This knowledge deficit is partly due to technical difficulties in obtaining useful transcriptomic data from the pituitary gland, namely, its small size during development and cellular complexity in maturity. Here we utilise high-sensitivity RNA sequencing at the embryonic stages, and single-cell RNA sequencing data to describe the imprinted transcriptome of the pituitary gland. In concert, we provide a comprehensive literature review of the current knowledge of the role of imprinted genes in pituitary hormonal pathways and how these relate to IDs. We present new data that implicate imprinted gene networks in the development of the gland and in the stem cell compartment. Furthermore, we suggest novel roles for individual imprinted genes in the aetiology of IDs. Finally, we describe the dynamic regulation of imprinted genes in the pituitary gland of the pregnant mother, with implications for the regulation of maternal metabolic adaptations to pregnancy.

Maternal nutrient restriction in late pregnancy programs postnatal metabolism and pituitary development in beef heifers.

Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. Therefore, an experiment was conducted to evaluate postnatal growth, metabolism, and development of beef heifers exposed to late gestation maternal nutrient restriction. Pregnancies were generated via transfer of in vitro embryos produced using X-bearing sperm from a single Angus sire. Pregnant dams were randomly assigned to receive either 100% (control; n = 9) or 70% (restricted; n = 9) of their total energy requirements from gestational day 158 to parturition. From post-natal day (PND) 301 until slaughter (PND485), heifers were individually fed ad libitum in a Calan gate facility. Calves from restricted dams were lighter than controls at birth (P<0.05) through PND70 (P<0.05) with no difference in body weight from PND105 through PND485 (P>0.10). To assess pancreatic function, glucose tolerance tests were performed on PND315 and PND482 and a diet effect was seen with glucose area under the curve being greater (P<0.05) in calves born to restricted dams compared to controls. At slaughter, total internal fat was greater (P<0.05) in heifers born to restricted dams, while whole pituitary weight was lighter (P<0.05). Heifers from restricted dams had fewer growth hormone-positive cells (somatotrophs) compared to controls (P<0.05). Results demonstrate an impaired ability to clear peripheral glucose in heifers born to restricted dams leading to increased deposition of internal fat. A reduction in the number of somatotrophs may contribute to the adipogenic phenotype of heifers born to restricted dams due to growth hormone's known anabolic roles in growth, lipolysis, and pancreatic islet function.

Oral contraceptive use is associated with smaller hypothalamic and pituitary gland volumes in healthy women: A structural MRI study.

The effects of hormonal contraceptives on structural features of the hypothalamus and pituitary are incompletely understood. One prior study reported microstructural changes in the hypothalamus with oral contraceptive pill (OCP) use. However, effects on hypothalamic volume have not been reported. One prior study reported volumetric changes in the pituitary. However, this study was limited by including participants evaluated for neurological symptoms. We sought to determine if OCP use is associated with alteration of hypothalamic or pituitary volume. High-resolution 3T MRI was performed for a prospective cohort of 50 healthy women from 2016 to 2018, which comprised 21 OCP users (age, 19-29) and 29 naturally cycling women (age, 18-36). Participants were excluded if they were pregnant or had significant medical conditions including neurological, psychiatric, and endocrine disorders. After confirming reliability of the image analysis techniques, 5 raters independently performed manual segmentation of the hypothalamus and semi-automated intensity threshold-based segmentation of the pituitary using ITK-SNAP. Total intracranial volume was estimated using FreeSurfer. A general linear model tested the association of OCP use with hypothalamic and pituitary volumes. Hypothalamic (B = -81.2 ± 24.9, p = 0.002) and pituitary (B = -81.2 ± 38.7, p = 0.04) volumes in OCP users were smaller than in naturally cycling women. These findings may be related to interference with known trophic effects of sex hormones and suggest a structural correlate of central OCP effects.

A mouse model of BBS identifies developmental and homeostatic effects of BBS5 mutation and identifies novel pituitary abnormalities.

Primary cilia are critical sensory and signaling compartments present on most mammalian cell types. These specialized structures require a unique signaling protein composition relative to the rest of the cell to carry out their functions. Defects in ciliary structure and signaling result in a broad group of disorders collectively known as ciliopathies. One ciliopathy, Bardet-Biedl syndrome (BBS; OMIM 209900), presents with diverse clinical features, many of which are attributed to defects in ciliary signaling during both embryonic development and postnatal life. For example, patients exhibit obesity, polydactyly, hypogonadism, developmental delay and skeletal abnormalities along with sensory and cognitive deficits, but for many of these phenotypes it is uncertain, which are developmental in origin. A subset of BBS proteins assembles into the core BBSome complex, which is responsible for mediating transport of membrane proteins into and out of the cilium, establishing it as a sensory and signaling hub. Here, we describe two new mouse models for BBS resulting from a targeted LacZ gene trap allele (Bbs5-/-) that is a predicted congenital null mutation and conditional (Bbs5flox/flox) allele of Bbs5. Bbs5-/- mice develop a complex phenotype consisting of increased pre-weaning lethality craniofacial and skeletal defects, ventriculomegaly, infertility and pituitary anomalies. Utilizing the conditional allele, we show that the male fertility defects, ventriculomegaly and pituitary abnormalities are only present when Bbs5 is disrupted prior to postnatal day 7, indicating a developmental origin. In contrast, mutation of Bbs5 results in obesity, independent of the age of Bbs5 loss.

MECHANISMS IN ENDOCRINOLOGY: Pioneer transcription factors in pituitary development and tumorigenesis.

Pioneer transcription factors have key roles in development as master regulators of cell fate specification. Only a small fraction of all transcription factors have the pioneer ability that confers access to target genomic DNA sites embedded in so-called 'closed' heterochromatin. This ability to seek and bind target sites within the silenced portion of the epigenome is the basis for their role in changing cell fate. Upon binding heterochromatin sites, pioneer factors trigger remodeling of chromatin from a repressed into an active organization. This action is typically exerted at enhancer regulatory sequences, thus allowing activation of new gene subsets. During pituitary development, the only pioneer with a well-documented role is Pax7 that specifies the intermediate lobe melanotrope cell fate. In this review, a particular focus is placed on this Pax7 function but its properties are also considered within the general context of pioneer factor action. Given their potent activity to reprogram gene expression, it is not surprising that many pioneers are associated with tumor development. Overexpression or chromosomal translocations leading to the production of chimeric pioneers have been implicated in different cancers. We review here the current knowledge on the mechanism of pioneer factor action.

Conserved roles of Rax/rx3 genes in hypothalamus and pituitary development.

Rax (Rx) genes encode paired-type homeodomain-containing transcription factors present in virtually all metazoan groups. In vertebrates, studies in fish, amphibian, chick and mouse models have revealed that these genes play important roles in the development of structures located at the anterior portion of the central nervous system, in particular the eyes, the hypothalamus and the pituitary gland. In addition, human patients with eye and brain defects carry mutations in the two human Rax paralogues, RAX and RAX2. Here, we review work done in the last years on Rax genes, focusing especially on the function that mouse Rax and its zebrafish homologue, rx3, play in hypothalamic and pituitary development. Work on both of these model organisms indicate that Rax genes are necessary for the patterning, growth and differentiation of the hypothalamus, in particular the ventro-tuberal and dorso-anterior hypothalamus, where they effect their action by controlling expression of the secreted signalling protein, Sonic hedgehog (Shh). In addition, Rax/rx3 mutations disturb the development of the pituitary gland, mimicking phenotypes observed in human subjects carrying mutations in the RAX gene. Thus, along with their crucial role in eye morphogenesis, Rax genes play a conserved role in the development of the hypothalamus and adjacent structures in the vertebrate clade.

Requirement of FAT and DCHS protocadherins during hypothalamic-pituitary development.

Pituitary developmental defects lead to partial or complete hormone deficiency and significant health problems. The majority of cases are sporadic and of unknown cause. We screened 28 patients with pituitary stalk interruption syndrome (PSIS) for mutations in the FAT/DCHS family of protocadherins that have high functional redundancy. We identified seven variants, four of which putatively damaging, in FAT2 and DCHS2 in six patients with pituitary developmental defects recruited through a cohort of patients with mostly ectopic posterior pituitary gland and/or pituitary stalk interruption. All patients had growth hormone deficiency and two presented with multiple hormone deficiencies and small glands. FAT2 and DCHS2 were strongly expressed in the mesenchyme surrounding the normal developing human pituitary. We analyzed Dchs2-/- mouse mutants and identified anterior pituitary hypoplasia and partially penetrant infundibular defects. Overlapping infundibular abnormalities and distinct anterior pituitary morphogenesis defects were observed in Fat4-/- and Dchs1-/- mouse mutants but all animal models displayed normal commitment to the anterior pituitary cell type. Together our data implicate FAT/DCHS protocadherins in normal hypothalamic-pituitary development and identify FAT2 and DCHS2 as candidates underlying pituitary gland developmental defects such as ectopic pituitary gland and/or pituitary stalk interruption.

Development of the Pituitary Gland.

The development of the anterior pituitary gland occurs in distinct sequential developmental steps, leading to the formation of a complex organ containing five different cell types secreting six different hormones. During this process, the temporal and spatial expression of a cascade of signaling molecules and transcription factors plays a crucial role in organ commitment, cell proliferation, patterning, and terminal differentiation. The morphogenesis of the gland and the emergence of distinct cell types from a common primordium are governed by complex regulatory networks involving transcription factors and signaling molecules that may be either intrinsic to the developing pituitary or extrinsic, originating from the ventral diencephalon, the oral ectoderm, and the surrounding mesenchyme. Endocrine cells of the pituitary gland are organized into structural and functional networks that contribute to the coordinated response of endocrine cells to stimuli; these cellular networks are formed during embryonic development and are maintained or may be modified in adulthood, contributing to the plasticity of the gland. Abnormalities in any of the steps of pituitary development may lead to congenital hypopituitarism that includes a spectrum of disorders from isolated to combined hormone deficiencies including syndromic disorders such as septo-optic dysplasia. Over the past decade, the acceleration of next-generation sequencing has allowed for rapid analysis of the patient genome to identify novel mutations and novel candidate genes associated with hypothalmo-pituitary development. Subsequent functional analysis using patient fibroblast cells, and the generation of stem cells derived from patient cells, is fast replacing the need for animal models while providing a more physiologically relevant characterization of novel mutations. Furthermore, CRISPR-Cas9 as the method for gene editing is replacing previous laborious and time-consuming gene editing methods that were commonly used, thus yielding knockout cell lines in a fraction of the time. © 2020 American Physiological Society. Compr Physiol 10:389-413, 2020.

Genome-Wide Analysis and Function Prediction of Long Noncoding RNAs in Sheep Pituitary Gland Associated with Sexual Maturation.

Long noncoding RNA (lncRNA) plays a crucial role in the hypothalamic-pituitary-testis (HPT) axis associated with sheep reproduction. The pituitary plays a connecting role in the HPT axis. However, little is known of their expression pattern and potential roles in the pituitary gland. To explore the potential lncRNAs that regulate the male sheep pituitary development and sexual maturation, we constructed immature and mature sheep pituitary cDNA libraries (three-month-old, TM, and nine-month-old, NM, respectively, n = 3) for lncRNA and mRNA high-throughput sequencing. Firstly, the expression of lncRNA and mRNA were comparatively analyzed. 2417 known lncRNAs and 1256 new lncRNAs were identified. Then, 193 differentially expressed (DE) lncRNAs and 1407 DE mRNAs were found in the pituitary between the two groups. Moreover, mRNA-lncRNA interaction network was constructed according to the target gene prediction of lncRNA and functional enrichment analysis. Five candidate lncRNAs and their targeted genes HSD17B12, DCBLD2, PDPK1, GPX3 and DLL1 that enriched in growth and reproduction related pathways were further filtered. Lastly, the interaction of candidate lncRNA TCONS_00066406 and its targeted gene HSD17B12 were validated in in vitro of sheep pituitary cells. Our study provided a systematic presentation of lncRNAs and mRNAs in male sheep pituitary, which revealed the potential role of lncRNA in male reproduction.

Pubertal hormones predict sex-specific trajectories of pituitary gland volume during the transition from childhood to adolescence.

Pituitary gland volume (PGV) increases during childhood and adolescence in a sex-specific manner, and previous research suggests that puberty may be associated with PGV development. However, existing research to date has focused on sex hormones associated with gonadarche. Given the role of the pituitary gland in hypothalamic-pituitary-adrenal (HPA) axis function, the present study investigated associations between PGV development and HPA hormones that play a role in the earlier pubertal phase of adrenarche. Participants were a community sample of 249 children and early adolescents who participated in longitudinal brain imaging and pubertal assessments. Each participant provided data at one or two waves 1.5-3 years apart, resulting in 409 datasets that covered the age range 8-13 years. PGV was estimated from T1-weighted Magnetic Resonance Imaging (MRI) scans, and dehydroepiandrosterone (DHEA), its sulfate (DHEA-S) and testosterone were measured from saliva. Estradiol was measured for a subset of females. Parents reported on physical pubertal development. Linear mixed modeling was used to investigate associations between age, pubertal measures and PGV development. DHEA, DHEA-S and testosterone (in addition to physical maturation) explained variance in PGV development over and above age, and in a sex-dependent fashion. In all cases, associations were stronger, or only present in females. Estradiol was associated with PGV in females, but this did not appear to account for adrenarcheal hormone effects. Our findings suggest a key role for the hormones of adrenarche, the first biochemical phase of puberty, in PGV development. Further research is required to understand the sex-specific role of adrenarcheal and gonadarcheal hormones on the PGV across development.

Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine.

Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.

Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor.

BACKGROUND: Gonadotrope lineage differentiation is a stepwise process taking place during pituitary development. The early step of gonadotrope lineage specification is characterized by the expression of the Nr5a1 transcription factor, a crucial factor for gonadotrope cell fate determination. Abnormalities affecting Nr5a1 expression lead to hypogonadotropic hypogonadism and infertility. Although significant knowledge has been gained on the signaling and transcriptional events controlling gonadotrope differentiation, epigenetic mechanisms regulating Nr5a1 expression during early gonadotrope lineage specification are still poorly understood. RESULTS: Using ATAC chromatin accessibility analyses on three cell lines recapitulating gradual stages of gonadotrope differentiation and in vivo on developing pituitaries, we demonstrate that a yet undescribed enhancer is transiently recruited during gonadotrope specification. Using CRISPR/Cas9, we show that this enhancer is mandatory for the emergence of Nr5a1 during gonadotrope specification. Furthermore, we identify a highly conserved estrogen-binding element and demonstrate that the enhancer activation is dependent upon estrogen acting through ERα. Lastly, we provide evidence that binding of ERα is crucial for chromatin remodeling of Nr5a1 enhancer and promoter, leading to RNA polymerase recruitment and transcription. CONCLUSION: This study identifies the earliest regulatory sequence involved in gonadotrope lineage specification and highlights the key epigenetic role played by ERα in this differentiation process.

Some aspects of the hypothalamic and pituitary development, metamorphosis, and reproductive behavior as studied in amphibians.

In this review article, information about the development of the hypothalamo-hypophyseal axis, endocrine control of metamorphosis, and hormonal and pheromonal involvements in reproductive behavior in some amphibian species is assembled from the works conducted mainly by our research group. The hypothalamic and pituitary development was studied using Bufo embryos and larvae. The primordium of the epithelial hypophysis originates at the anterior neural ridge and migrates underneath the brain to form a Rathke's pouch-like structure. The hypothalamo-hypophyseal axis develops under the influence of thyroid hormone (TH). For the morphological and functional development of the median eminence, which is a key structure in the transport of regulatory hormones to the pituitary, contact of the adenohypophysis with the undeveloped median eminence is necessary. For the development of proopiomelanocortin-producing cells, contact of the pituitary primordium with the infundibulum is required. The significance of avascularization in terms of the function of the intermediate lobe of the pituitary was evidenced with transgenic Xenopus frogs expressing a vascular endothelial growth factor in melanotropes. Metamorphosis progresses via the interaction of TH, adrenal corticosteroids, and prolactin (PRL). We emphasize that PRL has a dual role: modulation of the speed of metamorphic changes and functional development of organs for adult life. A brief description about a novel type of PRL (1B) that was detected was made. A possible reason why the main hypothalamic factor that stimulates the release of thyrotropin is not thyrotropin-releasing hormone, but corticotropin-releasing factor is considered in light of the fact that amphibians are poikilotherms. As regards the reproductive behavior in amphibians, studies were focused on the courtship behavior of the newt, Cynops pyrrhogaster. Male newts exhibit a unique courtship behavior toward sexually developed conspecific females. Hormonal interactions eliciting this behavior and hormonal control of the courtship pheromone secretion are discussed on the basis of our experimental results.

Comparative transcriptomic analysis of hypothalamus-pituitary-liver axis in bighead carp (Hypophthalmichthys nobilis) with differential growth rate.

BACKGROUND: Growth rate is one of the most important features for aquaculture species and deciphering its regulation mechanism has great significance both in genetics and in economics. Hypothalamus-pituitary growth axis (HP growth axis) or neuro-endocrine axis plays a vital role in growth regulation in different aquaculture animals. RESULTS: In this study, the HP and liver transcriptomes of two female groups (H and L) with phenotypically extreme growth rate were sequenced using RNA-Seq. A total of 30,524 and 22,341 genes were found expressed in the two tissues, respectively. The average expression levels for the two tissues were almost the same, but the median differed significantly. A differential expression analysis between H and L groups identified 173 and 204 differentially expressed genes (DEGs) in HP and liver tissue, respectively. Pathway analysis revealed that DEGs in HP tissue were enriched in regulation of cell proliferation and angiogenesis while in liver tissue these genes were overrepresented in sterol biosynthesis and transportation. Genomic overlapping analyses found that 4 and 5 DEGs were within growth-related QTL in HP and liver tissue respectively. A deeper analysis of these 9 genes revealed 3 genes were functionally linked to the trait of interest. The expression of 2075 lncRNAs in HP tissue and 1490 in liver tissue were also detected, and some of lncRNAs were highly expressed in the two tissues. CONCLUSIONS: Above all, the results of the present study greatly contributed to the knowledge of the regulation of growth and then assisted the design of new selection strategies for bighead carp with improved growth-related traits.

Comparative Transcriptome Analysis Reveals Differentially Expressed Genes and Signaling Pathways Between Male and Female Red-Tail Catfish (Mystus wyckioides).

Sexual dimorphism is widespread in fish species. The red-tail catfish (Mystus wyckioides) is a commercially important catfish in the lower reaches of the Lancang River and the Mekong basin, and it shows a growth advantage in males. Here, RNA-seq was for the first time used to explore the gene expression difference between the sexes in the hypothalamus and pituitary of red-tail catfish, respectively. In the hypothalamus, 5732 and 271 unigenes have significantly higher and lower expressions, respectively, in males compared with females. KEGG analysis showed that 212 DEGs were annotated to 216 signaling pathways, and enrichment analysis suggested different levels of cAMP and glutamatergic synapse signaling between male and female hypothalami and some of the DEGs appear involved in gonad development and growth. In the pituitary, we found only 19 differentially expressed unigenes, which were annotated to 32 signaling pathways, most of which play important roles in gonad development.