Hormonal Treatments for Major Depressive Disorder: State of the Art.

Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis-based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis-based treatments of thyroid hormones (T3 and T4), and the HPG axis-based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.

Distinct nutritional and endocrine regulation of prothoracic gland activities underlies divergent life history strategies in Manduca sexta and Drosophila melanogaster.

Life history trade-offs lead to various strategies that maximize fitness, but the developmental mechanisms underlying these alternative strategies continue to be poorly understood. In insects, trade-offs exist between size and developmental time. Recent studies in the fruit fly Drosophila melanogaster have suggested that the steroidogenic prothoracic glands play a key role in determining the timing of metamorphosis. In this study, the nutrient-dependent growth and transcriptional activation of prothoracic glands were studied in D. melanogaster and the tobacco hornworm Manduca sexta. In both species, minimum viable weight (MVW) was associated with activation of ecdysteroid biosynthesis genes and growth of prothoracic gland cells. However, the timing of MVW attainment in M. sexta is delayed by the presence of the sesquiterpenoid hormone, juvenile hormone (JH), whereas in D. melanogaster it is not. Moreover, in D. melanogaster, the transcriptional regulation of ecdysteroidogenesis becomes nutrient-independent at the MVW/critical weight (CW) checkpoint. In contrast, in M. sexta, starvation consistently reduced transcriptional activation of ecdysteroid biosynthesis genes even after CW attainment, indicating that the nature of CW differs fundamentally between the two species. In D. melanogaster, the prothoracic glands dictate the timing of metamorphosis even in the absence of nutritional inputs, whereas in M. sexta, prothoracic gland activity is tightly coupled to the nutritional status of the body, thereby delaying the onset of metamorphosis before CW attainment. We propose that selection for survival under unpredictable nutritional availability leads to the evolution of increased modularity in both morphological and endocrine traits.

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome.

Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial. A role for the immunomodulatory consequences of oestrogen deficiency and altered adipokine production has been postulated. Altered levels of adipokines and dehydroepiandrosterone have been demonstrated in patients with NTM lung disease. Case reports of NTM lung disease in patients with hypopituitarism support the possibility that altered endocrine function influences disease susceptibility. This paper catalogues the evidence for immunomodulatory consequences of predicted endocrine changes in Lady Windermere syndrome, with emphasis on the immune response to NTM. Collectively, the data warrant further exploration of an endocrine link to disease susceptibility in Lady Windermere syndrome.

[Bone and metabolism]. / Os et métabolisme.

Bone is now considered as a particular endocrine organ. Its endocrine function is not yet fully understood and has been the subject of several conferences at the European Society of Endocrinology Congress 2018. Bone regulates phosphate metabolism by secreting fibroblast growth factor 23; it also regulates glucose metabolism via osteocalcin and energy metabolism, thanks to lipocalin 2, a new hormone acting on the brain. In addition, the incidence of diabetes continues to grow, and its impact on bone has been demonstrated, with an increased risk of fractures regardless the type of diabetes. The mechanism of bone fragility in this disease is not fully known but it involves a decrease in bone turnover and bone demineralization. Recent findings on the role of bone on glucose and mineral metabolism could open therapeutic perspectives, especially for the treatment of diabetes or obesity.

Measuring estrogens in women, men, and children: Recent advances 2012-2017.

The measurement of estrogens is important for diagnosing and monitoring the health of women, men, and children. For example, for postmenopausal women or women undergoing treatment for breast cancer with aromatase inhibitors, the measurement of extremely low concentrations of estrogens in serum, especially estradiol, is problematic but essential for proper medical care. Achieving superb analytical sensitivity and specificity has been and continues to be a challenge for the clinical laboratory, but is a challenge that is being taken seriously. Focusing on publications from 2012 to 2017, this review will provide an overview of recent research in the development of methods to accurately and precisely measure estrogens, including a variety of estrogen metabolites. Additionally, the latest in clinical research involving estrogen measurement in women, men, and children will be presented to provide an update on the association of estrogens with diseases or conditions such as breast cancer, precocious puberty, infertility, and pregnancy. This research update will provide context as to why estrogen measurement is important and why laboratories are working hard to support the recommendations made by the Endocrine Society regarding estrogen measurement.

THE ENDOCRINOLOGY OF AGING: A KEY TO LONGEVITY "GREAT EXPECTATIONS".

ABBREVIATIONS: AMP = adenosine monophosphate CETP = cholesteryl ester transfer protein FOXO = Forkhead box O GH = growth hormone HDL = high-density lipoprotein IGF-1 = insulin-like growth factor 1 LDL = low-density lipoprotein miRNA = microRNA mTOR = mammalian target of rapamycin SIRT = sirtuin T4 = thyroxine TSH = thyroid-stimulating hormone "The Moving Finger writes; and, having writ, Moves on: nor all thy Piety nor Wit Shall lure it back to cancel half a Line, Nor all thy Tears wash out a Word of it." Omar Khayyam ( 1 ).

[Changes in serum hormone levels in the middle and gerontic aged inhabitants of Arkhangelsk due to the gender identity].

The serum hormone levels were studied among middle and gerontic aged residents of Arkhangelsk by enzyme immunoassay and radioimmunoassay. The significant increase of follicle-stimulating and luteinizing hormones levels in gerontic aged men was recorded in the presence of higher concentrations of these hormones in women. There was a statistical tendency of decrease in the level of testosterone in gerontic aged women compared to middle aged. Regardless of gender the lowering of the dehydroepiandrosterone sulfate content was observed in gerontic aged residents compared to middle aged. The criteria of functional activity reduction of the thyroid gland were a decrease in serum free thyroxine fraction levels in gerontic aged women and low concentrations of common triiodothyronine in middle aged men living in Arkhangelsk. Serum cortisol, insulin, estradiol, growth hormone had no significant age and sex differences in the present groups. The number of correlations was greater among the gerontic aged people in comparison with the middle aged, especially among women.

Endocrine alterations from concentric vs. eccentric muscle actions: a brief review.

Resistance exercise has a positive effect on many tissues, including heart, bone, skeletal muscle, and nervous tissue. Eccentric muscle actions offer a unique and a potentially beneficial form of exercise for maintaining and improving health. During resistance exercise, the effects of gravity, and mechanical properties of the sarcomere and connective tissue in skeletal muscle allow a greater muscle load during an eccentric (lengthening) muscle contraction than a concentric (shortening) muscle contraction. Consequently, older patients, patients with muscle or limb movement limitations or injuries, as well as cancer patients may be able to benefit from isolated eccentric muscle actions. There are specific physiological responses to eccentric muscle contractions. This review will describe the effects of different eccentric muscle contraction protocols on endocrine responses that could have positive effects on different tissues and recommend direction for future research.

Case-based learning in endocrine physiology: an approach toward self-directed learning and the development of soft skills in medical students.

The Medical Council of India, in the recent Vision 2015 document, recommended curricular reforms for undergraduates. Case-based learning (CBL) is one method where students are motivated toward self-directed learning and to develop analytic and problem-solving skills. An overview of thyroid physiology was given in a didactic lecture. A paper-based case scenario of multinodular goiter was given to phase I Bachelor of Medicine, Bachelor of Surgery students in two sessions. An attitude survey of the students and teachers was done using a Likert scale ranging from strongly disagrees to strongly agree. A pretest and posttest were conducted. The students opined that CBL helped them to better their understanding of a particular topic, gave them better retention of knowledge, helped them to relate clinical conditions to basic sciences, improved soft skills such as communication skills and group dynamics, and promoted a better teacher-student relationship. There was significant improvement in student's performance when pre- and posttest scores were compared (P = 0.018). Furthermore, faculty members opined that CBL promoted self-study and problem-solving abilities of the students. In conclusion, CBL motivates students toward self-directed learning and to develop analytic and problem-solving skills; thus, CBL could be beneficial for students' entry into clinical departments and, finally, in managing patients.

Sensitization of endocrine organs to anterior pituitary hormones by the autonomic nervous system.

Hormone secretion from endocrine glands constitutes a primary component of homeostatic control systems that defend whole body tissue viability and function. Endocrine organ secretion is controlled by efferent mechanisms that consist of both hormonal and neural elements. Anatomical evidence for dual control has led to increased understanding of how autonomic neural activity modulates functional sensitivity to hormonal input. The clinical relevance of autonomic-endocrine interactions is illustrated by examining functional control of the adrenal cortex and the ovary, two tissues that require tropic support from the anterior pituitary and receive sympathetic neural input. Extrapituitary mechanisms of adrenal cortical control including sympathetic neural activity have been implicated in controlling the amplitude of the cortisol awakening response (CAR), a diagnostic index of hypothalamic-pituitary-adrenal activity in humans. In addition, increases in sympathetic neural tone have been implicated in polycystic ovary syndrome (PCOS), a leading cause of female infertility. These examples offer strong evidence for the capability of autonomic neural activity to alter the functional sensitivity of endocrine glands. This interaction has significant clinical relevance and needs to be incorporated into our view in assessing endocrine organ function and dysfunction.

Physiology of the female reproductive axis.

The female reproductive system contains two principal components: the uterus, which supports the developing fetus, and the ovaries, which produce the female gametes. This manuscript will review how the hypothalamus, pituitary, ovary and uterus are integrated into the female reproductive system. The endocrinology of pregnancy, as well as a cursory overview of reproductive pathology, will be presented in each section. In addition, the most common endocrinopathy in women, polycystic ovarian syndrome, as well as the early loss of reproductive function, premature ovarian failure, will receive special mention.

Assessment of long term endocrine function after transplantation of frozen-thawed human ovarian tissue to the heterotopic site: 10 year longitudinal follow-up study.

PURPOSE: To assess the longevity of ovarian grafts in five cancer patients who underwent heterotopic autotransplantation of frozen-thawed ovarian tissue. METHOD(S): Five cancer survivors underwent heterotopic ovarian transplantation between 2001 and 2011. Stored ovarian tissue (for 1-10 years) was rapidly thawed and transplanted into the space between the rectus sheath and the rectus muscle (8-20 cortical sections per patient). Endocrine function was assessed by monthly blood tests (FSH, LH, E2, progesterone and testosterone) and ultrasound after transplantation. The monitoring was continued until the cessation of endocrine function by consecutive blood tests (E2 < 20 pg/ml; FSH ≥ 35 IU/L). RESULT(S): Endocrine function was restored in all patients between 12-20 weeks after transplantation. Four patients required the second transplantation one to two years after the first transplantation. The duration of endocrine function after the second transplantation was much longer (9 months-84 months). The longest duration of endocrine function was seen in a woman who underwent ovarian transplantation in 2003 and 2004 after radiotherapy for cervical cancer. Even more than seven years after transplantation, endocrine function has not ceased (FSH 9.5, E2 108, on July 1, 2011). Of note, this patient underwent three IVF cycles in 2004 which resulted in four embryos. CONCLUSION(S): Long-term endocrine function lasting for seven years can be established with heterotopic transplantation of cryobanked human ovarian tissue. Re-establishment of long-term endocrine function after ovarian transplantation will benefit young cancer survivors with premature ovarian failure.

Morphologic analysis of mice’s pineal gland

The pineal gland or pineal body is an endocrine gland that constitutes an important part of the neuroendocrine system, due to the secretion of melatonin, a hormone responsible for the seasonal organization of several physiologic and behavioral events of an individual’s life. Experimental researches using animals such as rats, mice and rabbits are often found in the extensive specific literature but aspects related to the morphology of mice’s pineal gland are few. Concerning its small size, the present paper performed a microscopic analysis of serial median sagittal sections of the pineal gland of 13 (thirteen) Swiss mice. The pineal gland of Swissmice was found to be in the median plane below the splenium of the corpus callosus, superior and dorsal to the habenular commissure, and rostral to the rostral colliculi. The pineal gland is closely related to the third ventricle and presents itself with a characteristic tonsillar shape with a stalk. Two types of different cells were identified in the gland, that is, astrocytes and pinealocytes, spreading randomly all over the glandular tissue. Calcifications of the pineal gland were not found in any of the observed animals.

Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs.

Ex situ bioengineering is one of the most promising perspectives in the field of regenerative medicine allowing for organ reconstruction outside the living body; i.e. on the laboratory bench. A number of hollow viscera of the cardiovascular, respiratory, genitourinary, and digestive systems have been successfully bioengineered ex situ, exploiting biocompatible scaffolds with a 3D morphology that recapitulates that of the native organ (organomorphic scaffold). In contrast, bioengineering of entire soft tissue organs and, in particular endocrine glands still remains a substantial challenge. Primary reasons are that no organomorphic scaffolding for endocrine viscera have as yet been entirely assembled using biocompatible materials, nor is there a bioreactor performance capable of supporting growth within the thickness range of the regenerating cell mass which has proven to be reliable enough to ensure formation of a complete macroscopic gland ex situ. Current technical options for reconstruction of endocrine viscera include either biocompatible 3D reticular scaffolds lacking any organomorphic geometry, or allogenic/xenogenic acellular 3D matrices derived from a gland similar to that to be bioengineered, eventually recellularized by autologous/heterologous cells. In 2007, our group designed, using biocompatible material, an organomorphic scaffold-bioreactor unit for bioengineering ex situ the human thyroid gland, chosen as a model for its simple anatomical organization (repetitive follicular cavities). This unit reproduces both the 3D native geometry of the human thyroid stromal/vascular scaffold, and the natural thyrocyte/vascular interface. It is now under intense investigation as an experimental tool to test cellular 3D auto-assembly of thyroid tissue and its related vascular system up to the ex situ generation of a 3D macroscopic thyroid gland. We believe that these studies will lay the groundwork for a new concept in regenerative medicine of soft tissue and endocrine organs; i.e. that the organomorphism of a biocompatible scaffold-bioreactor complex is essential to both the 3D organization of seeded stem cells/precursor cells and their phenotypic fate as glandular/parenchymal/vascular elements, eventually leading to a physiologically competent and immuno-tolerant bioconstruct, macroscopically suitable for transplantation and clinical applications.

Tumor necrosis factor-α-induced inflammatory responses in cattle.

Tumor necrosis factor-alpha (TNF-α) is recognized as a cytokine because of its involvement in inflammation-mediated biological defense functions. Although TNF-α is primarily produced by macrophages, it is also produced by other cells, including lymphocytes, Kupffer cells, natural killer cells and adipocytes. While TNF-α has diverse immune system functions, including antitumor activity, antimicrobial activity and mediation of inflammation, it also regulates a number of physiological functions, including appetite, fever, energy metabolism and endocrine activity. Factors such as viruses, parasites, other cytokines, and endotoxins induce TNF-α production. In combination with other cytokines, TNF-α plays a clinically important role in cattle by mediating immune inflammatory responses such as mastitis and endotoxic shock. It has been reported that cytokines such as TNF-α are involved in metabolic disease such as acidosis. On the other hand, several data suggest that lactoferrin (LF) acts to prevent the release of a number of inflammatory mediators from various activated cells, and further suggest that the prophylactic effect of LF involves inhibition of cytokine production, including TNF-α, that are principal mediators of the inflammatory response leading to death from toxic shock. This review discusses the role of TNF-α in pathological conditions in cattle, including infections and metabolic diseases caused by perturbation of metabolism and endocrine functions.

Pituitary insufficiency after operation of supratentorial intra- and extraaxial tumors outside of the sellar-parasellar region?

Recent studies investigating pituitary function after non-sellar brain tumor surgery showed that up to 38.2% of patients have pituitary insufficiency (PI). It has been assumed that the operation causes the PI, but preoperative hormone testing, which would have been necessary to prove this assumption, was not performed. The objective of this study is to answer the question if indeed microsurgery is the culprit of PI in patients with operatively treated non-sellar brain tumors. In this prospective trial, 54 patients with supratentorial non-sellar tumors were included. The basal levels of cortisol, prolactin, testosterone, estrogen, IGF-1, fT3, fT4, STH, TSH, ACTH, FSH, and LH were recorded preoperatively on days 1 and 7 after surgery. If basal hormone screening revealed an abnormality, a releasing hormone assay was performed. Before surgery, 24 of the 54 patients (44.4%) already had PI. Additional 25 patients showed either hypocortisolism or hypothyreoidism. As those patients had been pre-treated with dexamethasone and L-thyroxine, these findings were considered not to represent PI but drug effects. Hormone testing on days 1 and 7 after surgery revealed no changes. With 44.4% PI is a frequent finding in brain tumor patients already before surgery. The factors causing preoperative PI remain yet to be identified. The endocrine results after surgery are unchanged which rules out that surgery is the cause of PI.