2013, the DNA jubilee year

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Pituitary hormone-producing cells after estradiol application in rat models of menopause

Female ageing represents the biological process of structural and functional changes in endocrine cells and tissues, as well as in pituitary hormone-producing cells. In addition to the hypothalamic releasing hormones, estradiol plays a significant role in the regulation of the synthesis/secretion of pituitary hormones and is still used therapeutically for menopausal symptoms. The effects of ageing or ovariectomy and synthetic estradiol application under these circumstances were evaluated in pituitary hormone-producing cells of female rats (animal models of menopause); i.e., the following cells were observed: gonadotropes (FSH and LH), thyrotropes (TSH), somatotropes (GH), mammotropes (PRL) and corticotropes (ACTH). The cells were immunostained and histologically analysed. The ELISA method was used for hormonal analyses. Ageing was found to cause diverse, commonly reductive changes regarding the volume, number and secretion of menopausal rat pituitary hormone- producing cells, except for PRL cells that exhibit significantly increased numbers and intensified secretion. After the treatment of middle-aged female rats with estradiol, the absolute and relative pituitary weights significantly increased in comparison with the control females. Histological parameters such as the cell and volume density of PRL and ACTH cells were significantly increased compared with the control values. The mentioned parameters of FSH, LH, GH, and occasionally TSH cells after estradiol treatment significantly decreased in comparison with the controls. The corresponding hormone levels followed the changes in the histological parameters. These data indicate that the application of estradiol to menopausal females may specifically, in two directions, modify the histological characteristics and secretory activities of different pituitary-hormone producing cells.Starenje kod ženskog pola je biološki proces tokom kojeg dolazi do promena u strukturi i funkciji endokrinih ćelija i tkiva, a posebnu osetljivost ispoljavaju hipofizne hormonprodukujuće ćelije. Pored oslobađajućih hormona hipotalamusa i estradiol ostvaruje zapaženu ulogu u regulaciji sinteze i sekrecije hipofiznih hormona, a još uvek se koristi u terapiji menopauzalnih tegoba. Efekti starenja ili ovarijektomije, kao i primene sintetskog estradiola pod tim okolnostima su ispitivani na hormon-produkujućim ćelijama hipofize ženki pacova srednjeg doba (animalni modeli menopauze) i to: gonadotropima (FSH i LH), tirotropima (TSH), somatotropima (GH), mamotropima (PRL) i kortikotropima (ACTH). Sve ćelije su imunohistohemijski bojene i histološki analizirane, dok je za određivanje nivoa hormona u krvi korišćena ELISA metoda. Utvrđeno je da starenje prouzrokuje različite, uglavnom reduktivne promene volumena, broja i sekrecije hormon-produkujućih ćelija hipofize u našim animalnim modelima menopauze, izuzev na primeru PRL ćelija čiji je broj značajno povećan, a sekrecija intenzivirana. Posle tretmana ženki pacova srednjeg doba estradiolom apsolutna i relativna masa hipofize je značajno povećana u poređenju sa kontrolnim ženkama. Histološki parametri poput volumena ćelija i volumenske gustine PRL i ACTH ćelija su značajno povećani u poređenju sa kontrolnim vrednostima. Sa druge strane, pomenuti parametri u FSH, LH i GH, a u izvesnim slučajevima i TSH ćelijama su značajno smanjeni nakon tretmana estradiolom, u poređenju sa kontrolama. Koncentracije odgovarajućih hormona u krvi su pratile navedene promene histoloških parametara. Ova zapažanja ukazuju da estradiol davan menopauzalnim jedinkama ženskog pola može na specifičan način, dvosmerno, modifikovati histološke karakteristike i sekretornu aktivnost različitih hormon-produkujućih ćelija hipofize.Projekat ministarstva br. 17300

Somatostatin acts by inhibiting pituitary TSH cells in female rats

The effects of intracerebroventricularly (i.c.v.) administered synthetic somatostatins (SRIH-14 and SRIH-28) on pituitary TSH cells of adult female rats were studied. The animals were i.c.v. injected with three 1.0 μg (5 μ1) doses of SRIH-14 or SRIH-28 every second day and sacrificed five days after the last dose. The controls received an equivalent volume of saline in the same manner according to the same schedule. The pituitary glands were excised and used for immunohistochemical and morphometric evaluation. The results obtained demonstrated a somatostatin-related decrease in relative pituitary weight. The morphometric analyzes showed decreased volumetric density of TSH-immunoreactive cells in SRIH-treated groups, but this difference was more expressed in SRIH-14- treated animals than in those receiving SRIH-28. On the basis of these results it can be concluded that centrally administered somatostatins inhibit TSH cells.Ispitivani su efekti intracerebroventrikularno (i.c.v.) injiciranih sintetičkih somatostatina (SRIH-14 i SRIH-28) na hipofizne TSH ćelije adultnih ženki pacova. Životinje su i.c.v. injicirane satri doze od po 1 μg SRIH-14 ili -28 rastvorenog u 5 pi fiziološkog rastvora svaki drugi dan, a žrtvovane 5 dana posle poslednje injekcije. Kontrole su tretirane odgovarajućom dozom fiziološkog rastvora. Hipofize su izolovane i pripremljene za imunocitohemijska i morfometrijska ispitivanja. Oba somatostatina izazivaju smanjenje relativne težine hipofize. Morfometrijska analiza pokazuje da je u obe tretirane grupe životinja volumenska gustina TSH-imunoreaktivnih ćelija smanjena te razlike su značajnije izražene u grupi životinja tretiranih sa SRIH-14 u odnosu na one tretirane sa SRIH-28. Na osnovu dobijenih rezultata možemo zaključiti da centralno aplikovani somatostatini inhibiraju TSH ćelije hipofize.nul

Reduced growth of the adrenal zona glomerulosa after neonatal treatment of female rats with SRIH-14

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Prenatal Glucocorticoids: Short-Term Benefits and Long-Term Risks

Glucocorticoids are steroid hormones synthesized in the adrenal gland cortex, and most of their physiological effects are mediated by the glucocorticoid receptor (GR), that acts as a ligand-dependent transcription factor. Coordinate changes in metabolism under glucocorticoid influence provide energy that is instantly and selectively available to vital organs, an enables them to deal with immediate environmental demands, at the expense of anabolic pathways, such as bone formation, reproduction, immunological responses and other, that are being blunted or delayed, under glucocorticoid influence [1-3]. During fetal development the synthesis of adrenal glucocorticoids precedes the establishment of a definitive structure of the gland. In rats, secretion of the main glucocorticoid – corticosterone starts as early as on day 13 of development [4] (term=22 days, short gestation period), while in humans secretion of the main glucocorticoid – cortisol starts in the 8th week of pregnancy (term=40 weeks, long gestation period) [5]. Glucocorticoid receptor mRNA is present in the tissue derivatives of all three germ layers from fetal day 13 onwards, and increases gradually during rat fetal development [6]. Human fetal tissues express GR at the gestational age of 6 weeks, meaning that the machinery for hormone action is prepared at the early stages of development [5]. These facts suggest that endogenous glucocorticoids produced by the fetal adrenal glands have a crucial role in fetal growth and the development of individual fetal tissues [7]. In response to the prepartum rise in glucocorticoids a wide variety of changes known as “preparation for birth” occurs, meaning that the maturational changes in many fetal tissues, essential for neonatal survival, are intensified during the last third of gestation. Namely, circulating glucocorticoids induce fetal lung maturation and surfactant production, trigger a variety of physiological effects on brain cell differentiation and synaptogenesis, stimulate the production of hepatic gluconeogenic enzymes, affect pancreatic -cell development and insulin content, influence renal development and affect the maturation of the immune system [8-10]. Metabolic, cardiovascular and immune adaptations under glucocorticoid influence are fundamental to successfully overcoming birth-related stress and postnatal adaptation of the newborn to environmental challenges [11, 12]. Environmental conditions influence the prevailing nutritional and endocrine status in mothers and fetuses. Numerous animal and human studies have shown that adverse environmental conditions during pregnancy, such as maternal undernutrition [13, 14], stress [15, 16], illness, placental insufficiency [17, 18], as well as prenatal glucocorticoid exposure [19, 20] affect fetal development and postnatal outcome. Changes in the maternal hypothalamic-pituitary-adrenal (HPA) activity, transplacental diffusion of nutrients, hormones and growth factor supply, potently affect the fetal HPA axis influencing glucocorticoid output as well as other developing systems [21, 22]. Gestational age, at which an insult occurs, its nature and intensity, determines the specific tissue or organ which will be affected by the insult. Glucocorticoids are the key mediators between maternal environment and the fetus, and as such are involved in adaptations of the fetus to predicted postnatal environment. Even transient changes in glucocorticoid levels could have longlasting consequences. The outcome might be growth retardation and change in the developmental trajectory, in the direction that best suited to the expected environment [23, 24]. This phenomenon is known as programming. The adaptations caused by suboptimal intrauterine conditions are appropriate if the predicted and actual postnatal environments match, and lead to survival to reproduce in a deprived environment [25, 26]. If there is a mismatch between the environment predicted and the actual environment experienced postnatally, adaptations are inappropriate and result in the development of disease like hypertension, ischemic heart disease, glucose intolerance, insulin resistance and type 2 diabetes [27-29]. In this chapter the latest findings, with clear statements from the literature, as well as own results regarding the endocrine mechanisms of intrauterine programming mediated by glucocorticoids will be analyzed. The causal relationship between a prenatally programmed endocrine axes and their postnatal functioning that affect growth, stress response, metabolism and reproduction will be discussed. In order to better understand mechanisms of fetal glucocorticoid programming of endocrine axes, special attention will be paid to key points of their development

The Morpho-Functional Parameters of Rat Pituitary Hormone Producing Cells after Genistein Treatment

Phytoestrogens are a diverse group of steroid-like compounds that occur naturally in many plants. There are various types of phytoestrogens, including the best-researched isoflavones which are commonly found in soy. The consumption of soy products has many health benefits, including protection against breast cancer, prostate cancer, menopausal symptoms, heart disease and osteoporosis. In contrast, use of hormonally active compounds-isoflavones may unfortunately interfere with the endocrine system and can have far-reaching consequences. Genistein, the most abundant soy-bean derived isoflavone, possesses a ring system similar to estrogens and acts through an estrogen receptor (ER)-mediated mechanism, by increasing or decreasing the transcription of ER-dependent target genes. Also, genistein can act on cells through ER non-dependent mechanisms, such as tyrosine kinase inhibitor. The neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, and stress responsiveness. It is well known, that estrogen is important for development of the neuroendocrine system in both sexes. At the pituitary level, estrogen is known to affect the regulation of all hormone producing (HP) cells, by direct and/or indirect mechanisms. Due to structural and functional resemblance to estrogen, the question may arise of whether and how genistein affects the morphofunctional features of pituitary HP cells. This review deals with the consequences of genistein’s effects on morphological, stereological and hormonal features of HP cells within the anterior pituitary gland. Transparency on this issue is needed because isoflavones are presently highly consumed. Inter alia, genistein as well as other isoflavones, are present in various dietary supplements and generally promoted as an accepted alternative to estrogen replacement therapy. Potential isoflavone biomedical exploitation is not only limited to estrogen replacement therapy, so it should be treated in a wider context of different ageing symptoms remediation

2013, the DNA jubilee year

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Immunohistochemical evidence for the presence of a Vasoactive Intestinal Peptide, Neuropeptide Y, and Substance P, in rat adrenal cortex after acute heat stress

Immunohistochemistry revealed the presence of Vasoactive Intestinal Peptide (VIP), Neuropeptide Y (NPY), and the absence of Substance P (SP) immunoreactivity in the rat adrenal cortex. VIP- and NPY-immunoreactivity were detected in nerve fibers around the small blood vessels projecting into the capsule and cortical zones surrounding blood vessels and cortical cells. After acute heat stress, VIP- and NPY-immunoreactivities in the nerve fibers were reduced, probably as a result of the release of these peptides

Pituitary hormone-producing cells after estradiol application in rat models of menopause

Female ageing represents the biological process of structural and functional changes in endocrine cells and tissues, as well as in pituitary hormone-producing cells. In addition to the hypothalamic releasing hormones, estradiol plays a significant role in the regulation of the synthesis/secretion of pituitary hormones and is still used therapeutically for menopausal symptoms. The effects of ageing or ovariectomy and synthetic estradiol application under these circumstances were evaluated in pituitary hormone-producing cells of female rats (animal models of menopause); i.e., the following cells were observed: gonadotropes (FSH and LH), thyrotropes (TSH), somatotropes (GH), mammotropes (PRL) and corticotropes (ACTH). The cells were immunostained and histologically analysed. The ELISA method was used for hormonal analyses. Ageing was found to cause diverse, commonly reductive changes regarding the volume, number and secretion of menopausal rat pituitary hormone- producing cells, except for PRL cells that exhibit significantly increased numbers and intensified secretion. After the treatment of middle-aged female rats with estradiol, the absolute and relative pituitary weights significantly increased in comparison with the control females. Histological parameters such as the cell and volume density of PRL and ACTH cells were significantly increased compared with the control values. The mentioned parameters of FSH, LH, GH, and occasionally TSH cells after estradiol treatment significantly decreased in comparison with the controls. The corresponding hormone levels followed the changes in the histological parameters. These data indicate that the application of estradiol to menopausal females may specifically, in two directions, modify the histological characteristics and secretory activities of different pituitary-hormone producing cells.Starenje kod ženskog pola je biološki proces tokom kojeg dolazi do promena u strukturi i funkciji endokrinih ćelija i tkiva, a posebnu osetljivost ispoljavaju hipofizne hormonprodukujuće ćelije. Pored oslobađajućih hormona hipotalamusa i estradiol ostvaruje zapaženu ulogu u regulaciji sinteze i sekrecije hipofiznih hormona, a još uvek se koristi u terapiji menopauzalnih tegoba. Efekti starenja ili ovarijektomije, kao i primene sintetskog estradiola pod tim okolnostima su ispitivani na hormon-produkujućim ćelijama hipofize ženki pacova srednjeg doba (animalni modeli menopauze) i to: gonadotropima (FSH i LH), tirotropima (TSH), somatotropima (GH), mamotropima (PRL) i kortikotropima (ACTH). Sve ćelije su imunohistohemijski bojene i histološki analizirane, dok je za određivanje nivoa hormona u krvi korišćena ELISA metoda. Utvrđeno je da starenje prouzrokuje različite, uglavnom reduktivne promene volumena, broja i sekrecije hormon-produkujućih ćelija hipofize u našim animalnim modelima menopauze, izuzev na primeru PRL ćelija čiji je broj značajno povećan, a sekrecija intenzivirana. Posle tretmana ženki pacova srednjeg doba estradiolom apsolutna i relativna masa hipofize je značajno povećana u poređenju sa kontrolnim ženkama. Histološki parametri poput volumena ćelija i volumenske gustine PRL i ACTH ćelija su značajno povećani u poređenju sa kontrolnim vrednostima. Sa druge strane, pomenuti parametri u FSH, LH i GH, a u izvesnim slučajevima i TSH ćelijama su značajno smanjeni nakon tretmana estradiolom, u poređenju sa kontrolama. Koncentracije odgovarajućih hormona u krvi su pratile navedene promene histoloških parametara. Ova zapažanja ukazuju da estradiol davan menopauzalnim jedinkama ženskog pola može na specifičan način, dvosmerno, modifikovati histološke karakteristike i sekretornu aktivnost različitih hormon-produkujućih ćelija hipofize.Projekat ministarstva br. 17300

The effects of somatostatins on the PRL cells in female rats

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