POMC mediates orofacial hyperalgesia under hypoestrogenic conditions.

Objective: The aim of the present study was to investigate the effectiveness of intensive short-term dynamic psychotherapy on pain perception and pain catastrophizing in women with breast cancer. Methods: In this quasi-experimental study, 30 women with breast cancer who referred to Imam Khomeini Hospital in Sari in 2024 were studied using convenience sampling. They were then randomly assigned to two groups: the short-term intensive psychodynamic intervention group (15 participants) and the control group (15 participants) without any intervention. The short-term intensive psychodynamic intervention was implemented according to the protocol by Teska et al. (2005) over 16 weekly sessions, each lasting one and a half hours. The samples were assessed at two stages, pre-test and post-test, using the Pain Perception Questionnaire by Schaal et al. (2010) and the Pain Catastrophizing Scale by Rahmati et al. (2017). Data were analyzed using repeated measures multivariate analysis of variance in SPSS24 software. Findings: In the intervention group, the mean scores for pain catastrophizing were (17.20±36.60) and for pain perception were (36.33±80.80) in the pre-test and post-test stages, respectively. Post-test scores significantly decreased compared to pre-test scores in the components of pain catastrophizing and pain perception in the experimental group compared to the control group. Additionally, the results showed that intensive short-term dynamic psychotherapy had a statistically significant effect on pain catastrophizing (P<0.05, F=24.41) and pain perception (P<0.05, F=56.201) after adjusting the means of the two groups based on the pre-test score. Conclusion: The results indicate the effectiveness of intensive short-term dynamic psychotherapy on pain catastrophizing and pain perception in women with breast cancer. Therefore, this therapy can be used alongside other medical treatment methods in hospitals and clinics dedicated to breast cancer patients to reduce the psychological needs and problems of women with this condition.

Colour polymorphism is widespread among vertebrates and plays important roles in prey–predator interactions, thermoregulation, social competition, and sexual selection. However, the genetic mechanisms involved in colour variation have been studied mainly in domestic mammals and birds, whereas information on wild animals remains scarce. Interestingly, the pro-opiomelanocortin gene (POMC) gives rise to melanocortin hormones that trigger melanogenesis (by binding the melanocortin-1-receptor; Mc1r) and other physiological and behavioural functions (by binding the melanocortin receptors Mc1-5rs). Owing to its pleiotropic effect, the POMC gene could therefore account for the numerous covariations between pigmentation and other phenotypic traits. We screened the POMC and Mc1r genes in 107 wild asp vipers (Vipera aspis) that can exhibit four discrete colour morphs (two unpatterned morphs: concolor or melanistic; two patterned morphs: blotched or lined) in a single population. Our study revealed a correlation between a single nucleotide polymorphism situated within the 3′-untranslated region of the POMC gene and colour variation, whereas Mc1r was not found to be polymorphic. To the best of our knowledge, we disclose for the first time a relationship between a mutation at the POMC gene and coloration in a wild animal, as well as a correlation between a genetic marker and coloration in a snake species. Interestingly, similar mutations within the POMC 3′-untranslated region are linked to human obesity and alcohol and drug dependence. Combined with our results, this suggests that the 3′-untranslated region of the POMC gene may play a role in its regulation in distant vertebrates.

Pro-opiomelanocortin (POMC) mRNA was detected on paraffin sections by in situ hybridization (ISH) in corticotrophs of 12 nontumorous pituitaries, 11 functioning corticotroph, and 11 silent pituitary adenomas. ISH combined with immunocytochemistry for adrenocorticotrophic hormone (ACTH), a POMC-derived peptide, was also performed. ACTH immunoreactive cells of the anterior lobes and those invading the posterior lobe showed a high or moderate level of POMC mRNA that was not correlated with the intensity of ACTH immunoreactivity. Variable levels of POMC gene expression were present in Crooke's cells, corticotrophs suppressed by glucocorticoid excess. Most functioning corticotroph adenomas and silent subtype 1 adenomas had an intense hybridization signal and ACTH immunoreactivity. In silent subtype 2 and 3 adenomas, POMC mRNA had a diffuse low level or was absent; in these adenomas ACTH immunoreactivity was diffuse, restricted to some cells, or negative. The results indicate that POMC gene is expressed in both normal and suppressed nontumorous corticotrophs. Intense signals for POMC mRNA are found in most functioning corticotroph adenomas. The difference between POMC gene expression in silent 1 and silent 2 and 3 adenomas suggests that different mechanisms are responsible for the lack of endocrine activity.

The pro-opiomelanocortin (POMC) gene is expressed in a subset of hypothalamic and hindbrain neurons and in pituitary melanotrophs and corticotrophs. POMC neurons release the potent opioid beta-endorphin and several active melanocortins that control homeostasis and feeding behavior. POMC gene expression in the CNS is believed to be controlled by distinct cis-acting regulatory sequences. To analyze the transcriptional regulation of POMC in neuronal and endocrine cells, we produced transgenic mice carrying POMC27*, a transgene containing the entire 6 kb of the POMC transcriptional unit together with 13 kb of 5' flanking regions and 8 kb of 3' flanking regions. POMC27* was tagged with a heterologous 30 bp oligonucleotide in the third exon. In situ hybridization studies showed an accurate cell-specific pattern of expression of POMC27* in the arcuate nucleus and the pituitary. Hypothalamic mRNA-positive neurons colocalized entirely with beta-endorphin immunoreactivity. No ectopic transgenic expression was detected in the brain. Deletional analyses demonstrated that neuron-specific expression of POMC transgenes required distal 5' sequences localized upstream of the pituitary-responsive proximal cis-acting elements that were identified previously. POMC27* exhibited a spatial and temporal pattern of expression throughout development that exactly paralleled endogenous POMC. RNase protection assays revealed that POMC27* expression mimicked that of POMC in different areas of the CNS and most peripheral organs with no detectable ectopic expression. Hormonal regulation of POMC27* and POMC was identical in the hypothalamus and pituitary. These results show that distal 5' sequences of the POMC gene located between -13 and -2 kb target expression into the CNS of transgenic mice in a precise neuron-specific, developmentally and hormonally regulated manner.

A new hypothesis of sex-differences in temporomandibular disorders: Estrogen enhances hyperalgesia of inflamed TMJ through modulating voltage-gated sodium channel 1.7 in trigeminal ganglion?

TAp63 is a transcription factor that has been reported to be important for energy and glucose homeostasis. However, where and how TAp63 functions is unclear. Chow-fed mutant mice with TAp63 deleted from pro-opiomelanocortin (POMC) neurons showed normal body weight and glucose metabolism in both sex. However, HFD fed male and female mice that lack TAp63 from POMC neurons both showed glucose intolerance (GTT) and insulin resistance independent of body weight. Strikingly, deletion of TAp63 in POMC neurons confers “male-like” diet-induced obesity (DIO) to female mice, but does not affect DIO phenotypes in male mice. In contrast, overexpression of TAp63 in POMC neurons partially prevents DIO in male mice but not in female mice. Here we show that POMC neurons in female mice display higher neural activities and express higher POMC mRNAs compared to male counterparts, and both these enhancements in female POMC neurons are correlated to higher expression levels of TAp63. Further, we found that the deletion of TAp63 reduced POMC neuronal activity and diminished the sexual dimorphism of POMC neural activity by decreasing the responsiveness of ERα-positive POMC neurons to the ERα agonist. Finally, we found that TAp63 binds to the promoter of POMC gene and regulate POMC gene expression in POMC neurons. In addition, the expression of energy homeostasis related genes like SRC-1, ERα and TAp63 target genes Sirt1, AMPKα2, LKB1 were also decreased in mice lacking TAp63 in POMC neurons. Collectively, TAp63 in mature POMC neurons regulates glucose homeostasis and TAp63 is one key molecular driver for the sexual dimorphism in energy homeostasis. Disclosure C. Wang: None. Y. He: None. P. Xu: None. Y. Yang: None. Y. Xu: None.

Effects of 2 Physiotherapy Programs on Pain Perception, Muscular Flexibility, and Illness Impact in Women With Fibromyalgia: A Pilot Study

Proopiomelanocortin (POMC) is the polypeptide precursor of several biologically active melanocortin peptides that have important roles in the regulation of food intake and energy homeostasis, adrenal steroidogenesis, melanocyte stimulation, and immune modulation. Mutation of the POMC gene has been associated with adrenal insufficiency, early-onset obesity, and red hair pigmentation. We describe an Indian boy with secondary hypocortisolism, hyperphagia, early-onset obesity, and skin pigmentation problem. Genetics analysis revealed a novel homozygous mutation in the POMC gene (p.Arg86Term). The boy also had central hypothyroidism in addition to the secondary hypocortisolism. Genetics analysis for the POMC gene should be considered in patients with secondary hypocortisolism, early-onset obesity, and pigmentary problems.

ContextMechanisms underlying pituitary corticotroph adenoma adrenocorticotropin (ACTH) production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes.ObjectiveWe characterized the 5′ ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production.MethodsWe examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent corticotroph adenomas (SCAs) that immunostain for but do not secrete ACTH.ResultsWe identified a novel regulatory region located near the intron 2/exon 3 junction in the human POMC gene, which functions as a second promoter and an enhancer. In vitro experiments demonstrated that CREB binds the second promoter and regulates its transcriptional activity. The second promoter is highly methylated in SCAs, partially demethylated in normal pituitary tissue, and highly demethylated in pituitary and ectopic ACTH-secreting tumors. In contrast, the first promoter is demethylated in all POMC-expressing cells and is highly demethylated only in pituitary ACTH-secreting tumors harboring the ubiquitin-specific protease 8 (USP8) mutation. Demethylation patterns of the second promoter correlate with clinical phenotypes of Cushing disease.ConclusionWe identified a second POMC promoter regulated by methylation status in ACTH-secreting pituitary tumors. Our findings open new avenues for elucidating subcellular regulation of the hypothalamic-pituitary-adrenal axis and suggest the second POMC promoter may be a target for therapeutic intervention to suppress excess ACTH production.

Molecular cloning of proopiomelanocortin cDNA and multi-tissue mRNA expression in channel catfish

Role of Preoperative Gonadotropin-Releasing Hormone Agonist in Post-Operative Adhesion Formation After Myomectomy

The effect of frontal deafferentation of the medial basal hypothalamus on pro-opiomelanocortin (POMC) gene expression was studied in the intermediate lobe (IL) and anterior lobe (AL) of the pituitary gland in the absence and presence of corticosterone (CORT). The lesion in the basal hypothalamus removed neural inputs to the IL and induced the glucocorticoid receptor (GR) in this tissue. The GR was visualized in the denervated IL by immunocytochemistry. Induction of the GR had a slow onset and was detectable at 3 weeks after lesion, but not at one week after the lesion. In order to study the effect of IL denervation on pro-opiomelanocortin (POMC) gene expression, the level of messenger RNA specifically encoding POMC was measured 1 and 3 weeks after lesion, in the IL and AL. In adrenalectomized (ADX) animals, the changes in POMC mRNA levels were not significant 1 week after lesion in the IL. Three weeks after denervation there was a 3-fold decrease in POMC mRNA in the IL in ADX rats which was blocked by chronic CORT replacement via subcutaneously implanted pellets. In the AL, CORT reduced the level of POMC gene expression in both the lesioned and control animals. It is concluded that (1) removal of neural input induces GR in the denervated IL cells; (2) with the appearance of the GR, POMC gene expression in the IL becomes sensitive to circulating glucocorticoids; (3) under these conditions, CORT may stimulate POMC gene expression in the IL as opposed to its inhibitory effect in the AL.

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.

The disproportionate increase of temporomandibular disorders (TMD) in women strongly suggest a hormonal influence primarily rooted in estrogen activity. Inflammation mediated by estrogen may be through various mechanisms of action in the immune system, expression of estrogen receptors, and upregulation of voltage-gated sodium channels, or due to genetic variations called polymorphism. The temporomandibular joint (TMJ) contains estrogen receptors, which control how the joint experiences pain together with its ability to maintain a stable state. Estrogen levels decrease in post-menopause and menstrual periods and these states relate to higher pain intensity and decreased joint health through both inflammatory mechanisms and changes in sodium channel activity within trigeminal ganglia. The trigeminal ganglion is a cluster of nerve cell bodies located near the trigeminal nerve, within the skull that plays a crucial role in processing sensory information from the face. While the ganglion itself is not the source of pain in all cases, direct trigger to the ganglion produces unpleasant pain sensations. Women of reproductive age show susceptibility to disc displacement together with arthralgia effects that correlate with genetic variations in the estrogen receptor genes ESR1 and ESR2. The incidence of TMD increases among women who have polycystic ovary syndrome (PCOD) as it causes estrogen to remodel the extracellular matrix. Hormonal abnormalities, such as increased androgen levels and possibly decreased progesterone levels, are common in women with PCOS and can have an impact on the temporomandibular joint (TMJ) and surrounding tissues. TMD can develop and worsen as a result of these hormonal changes as well as possible inflammatory reactions. Therefore, hormonal status together with life stages of reproduction function as essential factors for managing TMD.

A reverse transcription polymerase chain reaction (RT-PCR) assay was developed to distinguish between full-length transcripts and functionally aberrant, truncated transcripts of the proopiomelanocortin (POMC) gene. This assay was applied to RNA obtained from the testes of rats and mice, to Percoll-purified primary mouse Leydig cells, and to various Leydig-derived cell lines. The results indicate a very low level of expression for the full-length transcripts in whole rodent testis, in mouse Leydig cells and in the MA10 cell line. In Leydig cells, the major transcripts of the POMC gene were the shorter, truncated transcripts where the regions corresponding to exons 1 and 2 are missing.