Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

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A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

Scientific Reports ◽

10.1038/s41598-021-84818-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Junko Okano ◽

Yuki Nakae ◽

Takahiko Nakagawa ◽

Miwako Katagi ◽

Tomoya Terashima ◽

...

Keyword(s):

Bone Marrow ◽

Underlying Mechanism ◽

Basal Cells ◽

Barrier Dysfunction ◽

Skin Injury ◽

Accelerated Proliferation ◽

Radiation Induced ◽

Bone Marrow Derived Cells ◽

Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

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Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

Frontiers in Endocrinology ◽

10.3389/fendo.2020.612396 ◽

2021 ◽

Vol 11 ◽

Author(s):

Codruţa Şoica ◽

Mirela Voicu ◽

Roxana Ghiulai ◽

Cristina Dehelean ◽

Roxana Racoviceanu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Treatment Options ◽

Active Role ◽

Structural Features ◽

Sex Hormone ◽

Ongoing Research ◽

New Treatment ◽

Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

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Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/7097797 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Binaya Wasti ◽

Zhifeng Chen ◽

Yi Ke ◽

Wen Tao Duan ◽

Shao-Kun Liu ◽

...

Keyword(s):

Severe Asthma ◽

Sex Hormones ◽

Human Body ◽

Therapeutic Potential ◽

Corticosteroid Treatment ◽

Sex Hormone ◽

Asthma Prevalence ◽

Term Survival

Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.

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Role of the Ovary in the Regulation of Sex Hormone Binding Globulin and Its Contribution to Peripheral Levels of Androstenedione

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0029-1210252 ◽

2009 ◽

Vol 82 (04) ◽

pp. 29-34 ◽

Cited By ~ 1

Author(s):

P. Bolufer ◽

P. Antonio ◽

R. Garcia ◽

J. Munoz ◽

A. Rodriguez ◽

...

Keyword(s):

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Plasticity of basal cells during postnatal development in the rat epididymis

Reproduction ◽

10.1530/rep-12-0510 ◽

2013 ◽

Vol 146 (5) ◽

pp. 455-469 ◽

Cited By ~ 27

Author(s):

Winnie W C Shum ◽

Eric Hill ◽

Dennis Brown ◽

Sylvie Breton

Keyword(s):

Epithelial Cells ◽

Postnatal Development ◽

Tight Junctions ◽

Vas Deferens ◽

Structural Plasticity ◽

Basal Cells ◽

Cytokeratin 5 ◽

Rat Epididymis ◽

Immunofluorescence Labeling

Our previous study has shown that basal cells sense luminal factors by forming a narrow body projection that can cross epithelial tight junctions. As a first step toward characterizing the structural plasticity of basal cells, in this study, we followed their appearance and morphology in the rat epididymis and vas deferens (VD) during postnatal development and examined their modulation by androgens in adulthood. Immunofluorescence labeling for cytokeratin 5 showed that basal cells are absent at birth. They progressively appear in a retrograde manner from the VD and cauda epididymis to the initial segments during the postnatal weeks PNW1–3. At the onset of differentiation, basal cells are in contact with the lumen and their nucleus is located at the same level as that of adjacent epithelial cells. Basal cells then position their nucleus to the base of the epithelium, and while some are still in contact with the lumen, others have a ‘dome-shaped’ appearance. At PNW5–6, basal cells form a loose network at the base of the epithelium, and luminal-reaching basal cells are rarely detected. The arrival of spermatozoa during PNW7–8 did not trigger the development of projections in basal cells. However, cells with a narrow luminal-reaching projection began to reappear between PNW8 and PNW12 in the corpus and the cauda. Treatment with flutamide from PNW10 to PNW12 significantly reduced the number of luminal-reaching basal cell projections. In summary, basal cells exhibit significant structural plasticity during differentiation. Fewer apical-reaching projections were detected after flutamide treatment in adulthood, indicating the role of androgens in the luminal-sensing function of basal cells.

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Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex

Molecular Biology of the Cell ◽

10.1091/mbc.12.6.1775 ◽

2001 ◽

Vol 12 (6) ◽

pp. 1775-1789 ◽

Cited By ~ 80

Author(s):

Bettina Peters ◽

Jutta Kirfel ◽

Heinrich Büssow ◽

Miguel Vidal ◽

Thomas M. Magin

Keyword(s):

Epidermolysis Bullosa ◽

Basal Cells ◽

Epidermolysis Bullosa Simplex ◽

Keratin 5 ◽

Neonatal Lethality ◽

Keratin Filaments ◽

Wide Range ◽

Skin Integrity

In human patients, a wide range of mutations in keratin (K) 5 or K14 lead to the blistering skin disorder epidermolysis bullosa simplex. Given that K14 deficiency does not lead to the ablation of a basal cell cytoskeleton because of a compensatory role of K15, we have investigated the requirement for the keratin cytoskeleton in basal cells by inactivating the K5 gene in mice. We report that the K5− / − mice die shortly after birth, lack keratin filaments in the basal epidermis, and are more severely affected than K14− / −mice. In contrast to the K14− / −mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5− / − mice. In addition, K5 and K14 mice differed with respect to tongue lesions. Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo. Our data indicate that K5 may be the natural partner of K15 and K17. We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients.

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