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Keywords = pituitary transcription factors

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12 pages, 7448 KiB  
Article
An Old New Friend: Folliculo-Stellate Cells in Pituitary Neuroendocrine Tumors
by Valeria-Nicoleta Nastase, Iulia Florentina Burcea, Roxana Ioana Dumitriu-Stan, Amalia Raluca Ceausu, Flavia Zara, Catalina Poiana and Marius Raica
Cells 2025, 14(13), 1019; https://doi.org/10.3390/cells14131019 - 3 Jul 2025
Viewed by 408
Abstract
Pituitary neuroendocrine tumors (PitNETs) represent a complex pathology based on numerous incompletely elucidated molecular mechanisms. Beyond tumor cells, analyzing the tumor microenvironment may help identify novel prognostic markers and therapies. A key component of this environment is the folliculo-stellate (FS) cell. We examined [...] Read more.
Pituitary neuroendocrine tumors (PitNETs) represent a complex pathology based on numerous incompletely elucidated molecular mechanisms. Beyond tumor cells, analyzing the tumor microenvironment may help identify novel prognostic markers and therapies. A key component of this environment is the folliculo-stellate (FS) cell. We examined FS cells in 77 PitNETs obtained by transsphenoidal surgery, using glial fibrillary acidic protein (GFAP) as an immunohistochemical marker. Immunohistochemistry for anterior pituitary hormones and transcription factors was performed to accurately classify the tumors. Our study included 19 somatotroph, 16 mammosomatotroph, 5 plurihormonal PIT-1 positive, 7 corticotroph, 14 gonadotroph, 11 unusual plurihormonal, and 5 null cell PitNETs. FS cells were observed in 55 of the cases, distributed isolated, in small groups or diffuse networks. A considerable number of tumors immunopositive for more than one hormone (including associations between GH/PRL, but also unusual combinations like GH/ACTH) also contained FS cells (p < 0.01), suggesting their involvement in tumor lineages differentiation. In 27 tumors, GFAP-positive cells clustered in highly vascularized areas. Additionally, in 11 of these cases a direct interaction between endothelial cells and FS cells was noted, sustaining their potential role in tumor angiogenesis. Given their complexity, FS cells may be crucial for understanding tumorigenesis mechanisms. Full article
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16 pages, 1419 KiB  
Review
Histopathological Types, Clinical Presentation, Imaging Studies, Treatment Strategies, and Prognosis of Posterior Pituitary Tumors: An Updated Review
by Pedro Iglesias
J. Clin. Med. 2025, 14(13), 4553; https://doi.org/10.3390/jcm14134553 - 26 Jun 2025
Viewed by 527
Abstract
Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal [...] Read more.
Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal pituicytoma. All share nuclear TTF-1 expression, confirming their common origin, but differ in morphology, immunophenotype, and ultrastructure. Histologically, pituicytomas consist of bipolar spindle cells in fascicles; granular cell tumors show polygonal cells with PAS-positive, diastase-resistant cytoplasmic granules; spindle cell oncocytomas display oncocytic change and abundant mitochondria; and ependymal pituicytomas exhibit perivascular pseudorosettes and EMA positivity in apical or dot-like patterns. Immunohistochemically, all are S100 and vimentin positive, and negative for pituitary hormones and lineage-specific transcription factors. Clinically, PPTs are typically non-functioning but may be associated with corticotroph or somatotroph hyperfunction. Imaging features are nonspecific. Surgical resection is the treatment of choice, although hypervascularity and adherence—especially in spindle cell oncocytomas—can hinder complete excision. Radiotherapy is reserved for recurrences. Molecular analyses reveal recurrent alterations in MAPK/PI3K pathways (e.g., HRAS, BRAF, FGFR1, NF1, TSC1) and suggest a shared histogenesis. Copy number imbalances correlate with reduced progression-free survival in some subtypes. Despite a generally favorable prognosis, recurrence—particularly in spindle cell oncocytomas—necessitates long-term follow-up. The WHO 2025 update provides a unified framework for classification, diagnosis, and prognostic stratification of these rare tumors. Full article
(This article belongs to the Section Oncology)
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29 pages, 3083 KiB  
Article
Synergistic Crosstalk of PACAP and Notch Signaling Pathways in Bone Development
by Vince Szegeczki, Andrea Pálfi, Csaba Fillér, Barbara Hinnah, Anna Tóth, Lili Sarolta Kovács, Adél Jüngling, Róza Zákány, Dóra Reglődi and Tamás Juhász
Int. J. Mol. Sci. 2025, 26(11), 5088; https://doi.org/10.3390/ijms26115088 - 26 May 2025
Viewed by 431
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that plays significant regulatory roles in the differentiation of the central nervous system and peripheral organs. A lack of the neuropeptide can lead to abnormalities in long bone development. In callus formation, a possible signaling [...] Read more.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that plays significant regulatory roles in the differentiation of the central nervous system and peripheral organs. A lack of the neuropeptide can lead to abnormalities in long bone development. In callus formation, a possible signaling balance shift in PACAP KO mice has been demonstrated, but Notch signalization, with its potential connection with PACAP 1-38, has not been investigated in ossification. Our main goal was to show connections between PACAP and Notch signaling in osteogenesis. Notch signalization showed an elevation in the long bones of PACAP-gene-deficient mice, and it was also elevated during the PACAP 1-38 treatment of UMR-106 and MC3T3-E1 osteogenic cells. Moreover, the inhibition of Notch signaling was compensated by the addition of PACAP 1-38 in vitro. The inorganic and organic matrix production of UMR-106 cells was increased during PACAP 1-38 treatment under the inhibition of Notch signaling. As a possible common target, the expression and nuclear translocation of NFATc1 transcription factor was increased during the disturbance of PACAP and Notch signaling. Our results indicate a possible synergistic regulation during bone formation by PACAP and Notch signalization. The crosstalk between Notch and PACAP signaling pathways highlights the complexity of bone development and homeostasis. Full article
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13 pages, 1065 KiB  
Review
Evidence for Pituitary Repression of the Human Growth Hormone-Related Placental Lactogen Genes and a Role for P Sequences
by Peter A. Cattini and Yan Jin
Int. J. Mol. Sci. 2025, 26(9), 4421; https://doi.org/10.3390/ijms26094421 - 6 May 2025
Viewed by 564
Abstract
The human (h) growth hormone (GH)/placental lactogen (PL) gene family has served as an important model to study tissue-specific expression. The two GH genes (hGH-N/GH1 and GH-V/GH2) and three PL or chorionic somatomammotropin hormone (CSH) genes ( [...] Read more.
The human (h) growth hormone (GH)/placental lactogen (PL) gene family has served as an important model to study tissue-specific expression. The two GH genes (hGH-N/GH1 and GH-V/GH2) and three PL or chorionic somatomammotropin hormone (CSH) genes (hPL-L/CSL1, hPL-A/CSH1 and hPL-B/CSH2) are clustered together at a single locus. Although they share >90% sequence similarity, hGH-N is expressed by somatotrophs of the anterior pituitary while the remaining four hGH/PL genes are expressed by the villous syncytiotrophoblast of the placenta. Efficient pituitary expression depends on a locus control region (LCR) that includes nuclease hypersensitive sites I-V (HS I-V). For activation, data indicate that HS III facilitates the initial access of pituitary-specific transcription factor Pit-1 to the locus, where it is required to bind Pit-1 sites at HS I/II and the hGH-N promoter. This is associated with histone acetylation and tri-methylation modifications that are consistent with active chromatin. However, all five hGH/PL genes share similar nuclease sensitivity in human pituitary chromatin, suggesting similar levels of accessibility and thus potential for transcription. Furthermore, hPL-A and hPL-B promoters contain Pit-1 binding sites, and the hPL-A promoter, like hGH-N, will support expression in transfected pituitary tumor GC cells in culture. These observations suggest the possibility of a transcriptional repressor mechanism that prevents hPL gene expression in the pituitary. P sequences were identified as a candidate. They are located upstream of all four placental hGH/PL genes but not hGH-N, repress hPL-A promoter activity in transfected pituitary GC cells, and bind a forkhead box A1/nuclear factor-1 transcription, which is proposed to act as a repressor complex in human pituitary chromatin. In spite of this, the inability to limit hGH-N expression when tested in transgenic mice brought the role of P sequences in pituitary repression into question. These observations are re-examined here in light of new evidence that the LCR (HS III) interacts with P sequences in the human pituitary. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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18 pages, 6289 KiB  
Article
Regulation of Immune-Related Gene Expression by Salinity-Induced HPI Axis in Large Yellow Croaker, Larimichthys crocea
by Jia Cheng, Zhengjia Lou, Huijie Feng, Yu Zhang, Honghui Li, Wuying Chu and Liangyi Xue
Int. J. Mol. Sci. 2025, 26(9), 4298; https://doi.org/10.3390/ijms26094298 - 1 May 2025
Viewed by 443
Abstract
Large yellow croaker is one of the most popular economic fish species in China. There are studies on the effects of salinity on the growth and development of large yellow croaker (Larimichthys crocea), but the effects of the hypothalamic–pituitary–interrenal axis (HPI), [...] Read more.
Large yellow croaker is one of the most popular economic fish species in China. There are studies on the effects of salinity on the growth and development of large yellow croaker (Larimichthys crocea), but the effects of the hypothalamic–pituitary–interrenal axis (HPI), HPI axis-related genes, and immune-related gene expression and its mechanisms have not been reported. This study analyzed the comparative transcriptomics of brain tissue in large yellow croaker under different salinity (12, 24, and 36 ppt) treatments for 4 weeks. The results showed that there were 1568 differential expression genes in the high salinity (HB) and normal salinity (NB) groups, including 494 up-regulated and 1074 down-regulated transcripts, and 1720 differential expression genes in the low salinity (LB) and normal salinity (NB) groups, including 486 up-regulated and 1234 down-regulated transcripts. Some pathways were significantly enriched, including the adrenergic signaling pathway of cardiomyocytes, oxidative phosphorylation, aldosterone synthesis and secretion, chemokine signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway. Quantitative Real-time polymerase chain reaction (qPCR) analysis further confirmed changes in the expression levels of HPI axis-related genes (β2-ADR, GH, and PRL) and significant changes in the expression levels of immune-related genes (IL6st, IL6, CXCL12, CD40, IFNAR1, SOCS2, SOCS6, and IRF1). In summary, this experiment demonstrates that salinity stress can activate the HPI axis and influence its immune function in large yellow croaker. Furthermore, the expression of immune factors during the immune response is regulated by the upstream genes of the HPI axis. The findings of this study are significant for understanding the physiological and immune responses of large yellow croaker to salinity stress. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 309 KiB  
Review
The Potential of Zebrafish Larvae and Water Vortex Protocols in Stress Biology
by Rodrigo J. De Marco
Endocrines 2025, 6(1), 11; https://doi.org/10.3390/endocrines6010011 - 4 Mar 2025
Viewed by 1282
Abstract
Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to [...] Read more.
Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to investigate hypothalamic–pituitary–interrenal (HPI) axis functionality during early development, advancing stress research while adhering to the 3Rs principle. Key publications are reviewed to discuss the potential of water vortices in zebrafish larvae for studying stress responses. These purely physical stressors exploit the innate positive rheotropism of developing zebrafish, offering precise control over timing and strength while avoiding confounding factors associated with chemical or biological interventions. The approach enables reproducible assessments of stress responses. The reviewed publications show advances in understanding cortisol response dynamics, glucocorticoid feedback, and early-life stress-induced changes in HPI axis function. Key findings include detailed cortisol patterns after acute stress, rapid glucocorticoid receptor-mediated feedback regulating cortisol levels, developmental shifts in HPI axis sensitivity, and reduced cortisol reactivity following early-life challenge (ELC). Vortex-driven ELC affects cortisol regulation, neuropeptide expression in the nucleus preopticus, and stress-related gene transcription. Combining zebrafish larvae and vortex protocols provides a robust and innovative platform for investigating stress biology. This approach leverages active, demanding behaviour to study stress mechanisms under controlled conditions, yielding insights with broad applications across vertebrate models while supporting the 3Rs principle. Future studies can build on these findings to address unresolved questions in stress regulation and enhance our understanding of adaptive physiological mechanisms. Full article
15 pages, 4572 KiB  
Review
Double PitNETs: A Case Report and Literature Review
by Mitsuru Nishiyama, Noriaki Fukuhara, Hiroshi Nishioka and Shozo Yamada
Cancers 2025, 17(4), 675; https://doi.org/10.3390/cancers17040675 - 17 Feb 2025
Viewed by 868
Abstract
Double pituitary neuroendocrine tumors (double PitNETs) are two distinct tumors in the same gland and are infrequent in clinical practice. In typical double PitNETs, an MRI detects two separate tumors that are diagnosed by pathology; they could also appear as a single tumor, [...] Read more.
Double pituitary neuroendocrine tumors (double PitNETs) are two distinct tumors in the same gland and are infrequent in clinical practice. In typical double PitNETs, an MRI detects two separate tumors that are diagnosed by pathology; they could also appear as a single tumor, and pathology would then identify the two independent tumors. A literature review was conducted, and 142 cases were analyzed to determine the characteristics of double PitNETs. Of these cases, acromegaly (45.5%) was the most common clinical feature, followed by Cushing’s disease (35.1%) and prolactinoma (17.9%), indicating that double PitNETs are usually noticed by hormonal excess symptoms due to at least one functional tumor. The pathological analysis of 284 tumors showed that somatotroph (28.9%) and corticotroph (26.8%) tumors were predominant, with a recent increase in the proportion of gonadotroph tumors. Regarding transcription factors, 51.1% were of GH-PRL-TSH PIT1-lineage, 26.1% ACTH TPIT-lineage, and 17.9% LH-FSH SF1-lineage. The radiological analysis of 82 cases revealed that double tumors (45.1%) and single tumors (47.6%) were comparable, suggesting that double PitNETs are often detected as a single tumor, and attention should be paid to hidden micro-tumors during surgery. Double PitNETs are complicated by a wide variety of clinical, radiological, and pathological findings, but diagnostic and therapeutic approaches are advancing. Full article
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20 pages, 649 KiB  
Article
Radiological and Immunohistochemical Characteristics of PitNETs in 79 Patients Undergoing Neurosurgery
by Anna Krzentowska, Ryszard Czepko, Dariusz Adamek, Michał Filipowicz, Elżbieta Broniatowska and Filip Gołkowski
Cancers 2025, 17(4), 666; https://doi.org/10.3390/cancers17040666 - 16 Feb 2025
Viewed by 607
Abstract
The human pituitary is a gland located within a small bony box, the sella turcica, under the base of the brain [...] Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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16 pages, 5341 KiB  
Article
Sex Differences in the Neuroendocrine Stress Response: A View from a CRH-Reporting Mouse Line
by Krisztina Horváth, Pál Vági, Balázs Juhász, Dániel Kuti, Szilamér Ferenczi and Krisztina J. Kovács
Int. J. Mol. Sci. 2024, 25(22), 12004; https://doi.org/10.3390/ijms252212004 - 8 Nov 2024
Viewed by 1791
Abstract
Corticotropin-releasing hormone (CRH) neurons within the paraventricular hypothalamic nucleus (PVH) play a crucial role in initiating the neuroendocrine response to stress and are also pivotal in coordination of autonomic, metabolic, and behavioral stress reactions. Although the role of parvocellular CRHPVH neurons in [...] Read more.
Corticotropin-releasing hormone (CRH) neurons within the paraventricular hypothalamic nucleus (PVH) play a crucial role in initiating the neuroendocrine response to stress and are also pivotal in coordination of autonomic, metabolic, and behavioral stress reactions. Although the role of parvocellular CRHPVH neurons in activation of the hypothalamic–pituitary–adrenal (HPA) axis is well established, the distribution and function of CRH-expressing neurons across the whole central nervous system are less understood. Stress responses activate complex neural networks, which differ depending on the type of stressor and on the sex of the individual. Because of the technical difficulties of localizing CRH neurons throughout the rodent brain, several CRH reporter mouse lines have recently been developed. In this study, we used Crh-IRES-Cre;Ai9 reporter mice to examine whether CRH neurons are recruited in a stressor- or sex-specific manner, both within and outside the hypothalamus. In contrast to the clear sexual dimorphism of CRH-mRNA-expressing neurons, quantification of CRH-reporting, tdTomato-positive neurons in different stress-related brain areas revealed only subtle differences between male and female subjects. These results strongly imply that sex differences in CRH mRNA expression occur later in development under the influence of sex steroids and reflects the limitations of using genetic reporter constructs to reveal the current physiological/transcriptional status of a specific neuron population. Next, we compared the recruitment of stress-related, tdTomato-expressing (putative CRH) neurons in male and female Crh-IRES-Cre;Ai9 reporter mice that had been exposed to predator odor. In male mice, fox odor triggered more c-Fos in the CRH neurons of the paraventricular hypothalamic nucleus, central amygdala, and anterolateral bed nucleus of the stria terminalis compared to females. These results indicate that male mice are more sensitive to predator exposure due to a combination of hormonal, environmental, and behavioral factors. Full article
(This article belongs to the Special Issue Emerging Molecular Views in Neuroendocrinology)
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11 pages, 5314 KiB  
Article
Identification of ActivinβA and Gonadotropin Regulation of the Activin System in the Ovary of Chinese Sturgeon Acipenser sinensis
by Huamei Yue, Huan Ye, Rui Ruan, Hao Du and Chuangju Li
Animals 2024, 14(16), 2314; https://doi.org/10.3390/ani14162314 - 9 Aug 2024
Viewed by 1201
Abstract
Activin is a dimeric growth factor with diverse biological activities in vertebrates. This study aimed to investigate the regulatory role of the activin signaling pathway in the ovary of the endangered, cultured sturgeon species Acipenser sinensis. One activinβA subunit was identified, with [...] Read more.
Activin is a dimeric growth factor with diverse biological activities in vertebrates. This study aimed to investigate the regulatory role of the activin signaling pathway in the ovary of the endangered, cultured sturgeon species Acipenser sinensis. One activinβA subunit was identified, with a full-length complementary DNA (cDNA) sequence of 1572 base pairs. Multiple sequence alignment suggested that ActivinβA shared high sequence identities with its counterparts in four other sturgeon species. Phylogenetic analysis indicated the conserved evolution of ActivinβA among vertebrates from mammals to fish species. Transcripts of activinβA were distributed ubiquitously in the liver, kidney, intestine, ovary, midbrain, hypothalamus, and pituitary, with the highest transcription found in the pituitary. In Chinese sturgeon ovarian cells, in vitro human recombinant Activin A incubation stimulated the activin system-related gene transcriptions of activinβA, follistatin, its receptors -activinRIIA and activinRIIB, and drosophila mothers against decapentaplegic proteins (smads) smad2, smad3, and smad4. Ovary development-related mRNA levels of cyp19a1a and aromatase receptors of erα and erβ were enhanced by Activin A or human chorionic gonadotropin (hCG) incubation. Furthermore, 15 IU/mL hCG treatment increased the transcription levels of activinβA, follistatin, activinRIIA, and smad2. This suggested that the activin system was functional for the regulation of ovary development in Chinese sturgeon, possibly under the regulation of gonadotropin, by recruiting activinβA, follistatin, activinRIIA, and smad2. These results were helpful for the molecular exploration of activin signaling in fish species, as well as the ovarian maturation regulation of A. sinensis. Full article
(This article belongs to the Section Animal Physiology)
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14 pages, 3669 KiB  
Article
Combined Pituitary Hormone Deficiency in lhx4-Knockout Zebrafish
by Nicole Roisman-Geller, Odelia Pisanty, Alon Weinberger, Deodatta S. Gajbhiye, Matan Golan and Yoav Gothilf
Int. J. Mol. Sci. 2024, 25(13), 7332; https://doi.org/10.3390/ijms25137332 - 4 Jul 2024
Cited by 1 | Viewed by 1511
Abstract
LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with LHX4 mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. Lhx4-knockout (KO) mice fail to develop [...] Read more.
LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with LHX4 mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. Lhx4-knockout (KO) mice fail to develop a normal AP and die shortly after birth. Here, we characterize a zebrafish lhx4-KO model to further investigate the importance of LHX4 in pituitary gland development and regulation. At the embryonic and larval stages, these fish express lower levels of tshb mRNA compared with their wildtype siblings. In adult lhx4-KO fish, the expressions of pituitary hormone-encoding transcripts, including growth hormone (gh), thyroid stimulating hormone (tshb), proopiomelanocortin (pomca) and follicle stimulating hormone (fshb), are reduced, the pomca promoter-driven expression in corticotrophs is dampened and luteinizing hormone (lhb)-producing gonadotrophs are severely depleted. In contrast to Lhx4-KO mice, Lhx4-deficient fish survive to adulthood, but with a reduced body size. Importantly, lhx4-KO males reach sexual maturity and are reproductively competent, whereas the females remain infertile with undeveloped ovaries. These phenotypes, which are reminiscent of those observed in CPHD patients, along with the advantages of the zebrafish for developmental genetics research, make this lhx4-KO fish an ideal vertebrate model to study the outcomes of LHX4 mutation. Full article
(This article belongs to the Special Issue Zebrafish as a Model in Human Disease: 3rd Edition)
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9 pages, 3163 KiB  
Article
A Nonsynonymous Substitution of Lhx3 Leads to Changes in Body Size in Dogs and Mice
by Wanyi Dang, Dali Gao, Guangqi Lyu, David M. Irwin, Songyang Shang, Junnan Chen, Junpeng Zhang, Shuyi Zhang and Zhe Wang
Genes 2024, 15(6), 739; https://doi.org/10.3390/genes15060739 - 4 Jun 2024
Viewed by 1217
Abstract
Lhx3 is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether Lhx3 plays a [...] Read more.
Lhx3 is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether Lhx3 plays a role in the differing body sizes of these three dog breeds, we sequenced the Lhx3 gene in the three breeds, which led to the identification of an SNP in codon 280 (S280N) associated with body size. The allele frequency at this SNP differed significantly between the large Akita and the two kinds of smaller Shiba dogs. To validate the function of this SNP on body size, we introduced this change into the Lhx3 gene of mice. Homozygous mutant mice (S279N+/+) were found to have significantly increased body lengths and weights compared to heterozygous mutant (S279N+/−) and wild-type (S279N−/−) mice several weeks after weaning. These results demonstrate that a nonsynonymous substitution in Lhx3 plays an important role in regulating body size in mammals. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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15 pages, 1662 KiB  
Article
Endocrine and Transcriptome Changes Associated with Testicular Growth and Differentiation in Atlantic Salmon (Salmo salar L.)
by Vetle Skjold, Sergey Afanasyev, Erik Burgerhout, Lene Sveen, Kjell-Arne Rørvik, Vasco Felipe Cardoso Neves Mota, Jens-Erik Dessen and Aleksei Krasnov
Curr. Issues Mol. Biol. 2024, 46(6), 5337-5351; https://doi.org/10.3390/cimb46060319 - 27 May 2024
Viewed by 1500
Abstract
Sexual maturation of Atlantic salmon males is marked by dramatic endocrine changes and rapid growth of the testes, resulting in an increase in the gonad somatic index (GSI). We examined the association of gonadal growth with serum sex steroids, as well as pituitary [...] Read more.
Sexual maturation of Atlantic salmon males is marked by dramatic endocrine changes and rapid growth of the testes, resulting in an increase in the gonad somatic index (GSI). We examined the association of gonadal growth with serum sex steroids, as well as pituitary and testicular gene expression levels, which were assessed with a DNA oligonucleotide microarray. The testes transcriptome was stable in males with a GSI < 0.08% despite the large difference between the smallest and the largest gonads. Fish with a GSI ≥ 0.23% had 7–17 times higher serum levels of five male steroids and a 2-fold increase in progesterone, without a change in cortisol and related steroids. The pituitary transcriptome showed an upregulation of the hormone-coding genes that control reproduction and behavior, and structural rearrangement was indicated by the genes involved in synaptic transmission and the differentiation of neurons. The observed changes in the abundance of testicular transcripts were caused by the regulation of transcription and/or disproportional growth, with a greater increase in the germinative compartment. As these factors could not be separated, the transcriptome results are presented as higher or lower specific activities (HSA and LSA). LSA was observed in 4268 genes, including many genes involved in various immune responses and developmental processes. LSA also included genes with roles in female reproduction, germinal cell maintenance and gonad development, responses to endocrine and neural regulation, and the biosynthesis of sex steroids. Two functional groups prevailed among HSA: structure and activity of the cilia (95 genes) and meiosis (34 genes). The puberty of A. salmon testis is marked by the predominance of spermatogenesis, which displaces other processes; masculinization; and the weakening of external regulation. Results confirmed the known roles of many genes involved in reproduction and pointed to uncharacterized genes that deserve attention as possible regulators of sexual maturation. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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18 pages, 2490 KiB  
Article
Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a tandem cAMP Response Element
by Lars Bürvenich, Oliver G. Rössler and Gerald Thiel
Curr. Issues Mol. Biol. 2024, 46(4), 3218-3235; https://doi.org/10.3390/cimb46040202 - 7 Apr 2024
Viewed by 1387
Abstract
The glycoprotein hormones LH, FSH, TSH and chorionic gonadotropin consist of a common α-subunit and a hormone-specific β-subunit. The α-subunit is expressed in the pituitary and the placental cells, and its expression is regulated by extracellular signal molecules. Much is known about the [...] Read more.
The glycoprotein hormones LH, FSH, TSH and chorionic gonadotropin consist of a common α-subunit and a hormone-specific β-subunit. The α-subunit is expressed in the pituitary and the placental cells, and its expression is regulated by extracellular signal molecules. Much is known about the regulation of the α-subunit gene in the pituitary, but few studies have addressed the regulation of this gene in trophoblasts. The aim of this study was to characterize the molecular mechanism of stimulus-induced α-subunit gene transcription in JEG-3 cells, a cellular model for human trophoblasts, using chromatin-embedded reporter genes under the control of the α-subunit promoter. The results show that increasing the concentration of the second messengers cAMP or Ca2+, or expressing the catalytic subunit of cAMP-dependent protein kinase in the nucleus activated the α-subunit promoter. Similarly, the stimulation of p38 protein kinase activated the α-subunit promoter, linking α-subunit expression to stress response. The stimulation of a Gαq-coupled designer receptor activated the α-subunit promoter, involving the transcription factor CREB, linking α-subunit expression to hormonal stimulation and an increase in intracellular Ca2+. Deletion mutagenesis underscores the importance of a tandem cAMP response element within the glycoprotein hormone α-subunit promoter, which acts as a point of convergence for a multiple signaling pathway. Full article
(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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17 pages, 7041 KiB  
Article
Three Copies of zbed1 Specific in Chromosome W Are Essential for Female-Biased Sexual Size Dimorphism in Cynoglossus semilaevis
by Yuqi Sun, Xihong Li, Jiaqi Mai, Wenteng Xu, Jiacheng Wang, Qi Zhang and Na Wang
Biology 2024, 13(3), 141; https://doi.org/10.3390/biology13030141 - 23 Feb 2024
Viewed by 1953
Abstract
The sex chromosome, especially specific in one sex, generally determines sexual size dimorphism (SSD), a phenomenon with dimorphic sexual difference in the body size. For Cynoglossus semilaevis, a flatfish in China, although the importance of chromosome W and its specific gene zbed1 in [...] Read more.
The sex chromosome, especially specific in one sex, generally determines sexual size dimorphism (SSD), a phenomenon with dimorphic sexual difference in the body size. For Cynoglossus semilaevis, a flatfish in China, although the importance of chromosome W and its specific gene zbed1 in female-biased SSD have been suggested, its family members and regulation information are still unknown. At present, three zbed1 copies gene were identified on chromosome W, with no gametologs. Phylogenetic analysis for the ZBED family revealed an existence of ZBED9 in the fish. Nine members were uncovered from C. semilaevis, clustering into three kinds, ZBED1, ZBED4 and ZBEDX, which is less than the eleven kinds of ZBED members in mammals. The predominant expression of zbed1 in the female brain and pituitary tissues was further verified by qPCR. Transcription factor c/ebpα could significantly enhance the transcriptional activity of zbed1 promoter, which is opposite to its effect on the male determinant factor-dmrt1. When zbed1 was interfered with, piwil1, esr2 and wnt7b were up-regulated, while cell-cycle-related genes, including cdk4 and ccng1, were down-regulated. Thus, zbed1 is involved in cell proliferation by regulating esr2, piwil1, cell cycle and the Wnt pathway. Further research on their interactions would be helpful to understand fish SSD. Full article
(This article belongs to the Section Marine Biology)
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