The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood. In this review, we will discuss the regulation of the HPA axis and its development. We will also examine the maternal-fetal hypothalamic-pituitary-adrenal axis and disruption of the normal fetal environment which becomes a major risk factor for many neurodevelopmental pathologies in adulthood, such as major depressive disorder, anxiety, schizophrenia, and others.

Chondroitin sulfate is referred as a symptomatic slow-acting drug for osteoarthritis because it improves articular function, and reduces joint swelling and effusion. In addition, chondroitin sulfate prevents joint space narrowing of the knee. We hypothesized that the anti-inflammatory effect of chondroitin sulfate is associated to a decrease in the activation of mitogen-activated protein kinases (MAPK) and of the transcription factors nuclear factor-κ B (NF-κ B) and activator protein-1 (AP-1). Cultured rabbit chondrocytes were stimulated with interleukin-1 β (IL-1 β ) in presence of chondroitin sulfate. Nuclear translocation of NF-κ B and AP-1, and nitrite concentrations (as an index for nitric oxide) was assessed 48 hr later. The effect of chondroitin sulfate on IL-1 β activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and p38MAPK was documented by immunoblot. The effect of chondroitin sulfate on sodium nitroprusside-induced apoptosis was evaluated with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay. Chondroitin sulfate reduced IL-1 β -induced NF-κ B nuclear translocation, but not AP-1 translocation, it decreased IL-1 β -induced phosphorylation of Erk1/2 and abrogated p38MAPK phosphorylation, but did not prevent IL-1 β -induced increase in nitrite. Finally, chondroitin sulfate decreased nitroprusside-induced apoptosis of the chondrocytes. These results suggest that some of the biological activities of chondroitin sulfate may be associated to the reduction in Erk1/2 and p38MAPK phosphorylation and nuclear transactivation of NF-κ B.

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Major depressive disorder topped ischemic heart disease as the number one cause of disability worldwide in 2012, and women have twice the risk of men. Further, the comorbidity of depression and cardiometabolic disorders will be one of the primary causes of disability worldwide by 2020, with women at twice the risk. Thus, understanding the sex-dependent comorbidities has public health consequences worldwide. We propose here that sex differences in MDD-cardiometabolic comorbidity originate, in part, from pathogenic processes initiated in fetal development that involve sex differences in shared pathophysiology between the brain, the vascular system, the CNS control of the heart and associated hormonal, immune, and metabolic physiology. Pathways implicate neurotrophic and angiogenic growth factors, gonadal hormone receptors, and neurotransmitters such as gamma amino butyric acid (GABA) on neuronal and vascular development of HPA axis regions, such as the paraventricular nucleus (PVN), in addition to blood pressure, in part through the renin-angiotensin system, and insulin and glucose metabolism. We show that the same prenatal exposures have consequences for sex differences across multiple organ systems that, in part, share common pathophysiology. Thus, we believe that applying a sex differences lens to understanding shared biologic substrates underlying these comorbidities will provide novel insights into the development of sex-dependent therapeutics. Further, taking a lifespan perspective beginning in fetal development provides the opportunity to target abnormalities early in the natural history of these disorders in a sex-dependent way.

The improvement in erectile function after brief aggressive treatment may be related to improvement in structurally based vascular resistance within the penis and the decrease in responsiveness of alpha1-adrenoceptor mediated erectolytic signaling. These findings are suggestive of a new therapeutic strategy for hypertension and erectile dysfunction.

No abstract

In hypertension, small arteries in a variety of vascular beds undergo structural changes that increase resistance. To assess whether there are differential structural changes in the penis that accompany hypertension, we began with determining structurally-based vascular resistance properties in penile and hindlimb vascular beds of adult spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats.In anesthetized SHR, the penile and hindlimb vasculature were isolated and perfused, maximum dilation was induced, and a¯ow-pressure assessment and a 1 -adrenoceptor agonist concentration-response curves were generated.Both the baseline and maximum constrictor responses were similar in the two beds of each strain, and overall the maximum structurally-based vascular resistance in SHR was higher than in SD rats.Our data suggests that the penile vasculature is not protected from the structural changes that take place in the other vascular beds in hypertension. There does not appear to be an underlying functional control mechanism that protects the penile vasculature from structural changes that may have a negative impact on penile blood¯ow.

The improvement in erectile function after brief aggressive treatment may be related to improvement in structurally based vascular resistance within the penis and the decrease in responsiveness of alpha1-adrenoceptor mediated erectolytic signaling. These findings are suggestive of a new therapeutic strategy for hypertension and erectile dysfunction.