Heat Shock Protein & Estrogen – PART 1

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Heat Shock Protein & Estrogen – PART 1

| By Nadine Shaban |

 

It wasn’t too long ago that I was sitting in my advisors office and he was giving me a lecture about some sort of life event.  His lectures about life still resonate with me after all this time.  I remember one particular story about one of his friends.  They were telling him how there was interest in getting a quote from him regarding a specific protein he researched; they wanted to put it on a supplement bottle.  This got me thinking about how much research and development is growing in the supplement industry.  And, as a result, so are the types of supplements landing on store shelves.

It seems like there is a new discovery about a certain amino acid, and/or protein daily.  And, enterprising supplement company owners rush to utilize the hype; throwing a bottle of whatever together and make some money.  This article is about a new supplement in town that actually works.  Don’t crap your pants looking for it, it isn’t on store shelves.  You can create this new supplement yourself.  You have permission to crap your pants now. Unfortunately it’s not as easy as popping a pill, but let me tell you it’s as COST EFFICIENT and you will get much more health benefits then one pill you pop.  Sit back, relax and enjoy my review on a protein called Heat Shock Protein (HspP70).

 

Warning: Nadine Shaban has just suffered a horrific lab accident; being bombarded with science gamma rays.  She has turned into the Science She-Hulk, smashing your brain with some science.

 

Science is uncovering gender differences that go beyond the reproductive and endocrine system.  Cardiovascular disease (CVD) is the major cause of death globally and will continue to escalate over the next decade.  More importantly, CVD is the leading cause of death in women, with diabetes greatly increasing this risk.  Scientific advances confirm the remarkable benefits of exercise, as it is well established that physical activity is an effective practice for reducing risks of many chronic diseases, such as Type 2 Diabetes (T2D) and CVD. For example, moderately intense physical activity (e.g., walking) reduces both CVD and T2D incidence rates, and decreases metabolic risk factors for developing CVD and T2D (5) (e.g., reduces blood pressure, improve lipid profiles in patients with T2D, and improves insulin sensitivity).

Premenopausal women have a cardio protective advantage over men, as estrogen can reduce the appearance and severity of CVD.   It is important to note that this protective barrier is attenuated in postmenopausal women, as estrogen levels decreased.  In contrast to this advantage, females are more likely to die when an incident transpires.  Interestingly, due to the estrogenic protection in combination with greater molecular advantages, premenopausal women require a greater stressor in order to induce a cardiovascular event.  Post trauma, females experience poorer outcomes, and are not able to return to their normal quality of life, compared to men as they have a better recovery process. Therefore, it may be more difficult for premenopausal women to develop CVD.  However, when they do, their recovery is more severe than males.  Nonetheless, premenopausal women encounter an unfortunate outcome in terms of physical activity as they do not attain the same protective benefits as males.  During exercise, estrogen may inhibit vital adaptations, including the expression of the cardio protective 70-kDa heat-shock protein, Hsp70.

Before I dig into the good stuff “Hsp70”, let’s take a step to look at why females rock and why when we work out and weight train we rock even more… not that I am biased or anything!

Before I dig into the good stuff “Hsp70”, let’s take a step to look at why females rock and why when we work out and weight train we rock even more… not that I am biased or anything!

 

UNDERSTANDING HOW ESTROGEN WORKS

Hormones are vital to the cellular function of the human body.  Estrogens are steroid hormones essential to the human endocrine system.  They have many diverse physiological, pathophysiological, and psychological functions in different tissues and cell types of both males and females.  Estrogen controls the development of essential reproductive organs, as well as aiding in maintaining homeostasis in specific organs.  It plays a key role in bone development, the central nervous system and in the cardiovascular system.  To add to its list of important functions; estrogen is a signaling molecule that stimulates critical enzymes, maintains cell function, and synthesizes many new proteins.

In the most basic manner, estrogen binds to its intracellular receptor located in the cytoplasm or nucleus.  Estrogen receptors (ER) have both a DNA binding domain, that activates transcriptional activity through hormone response elements, and a ligand binding domain.  Therefore, in the absence of estrogen, ER resides in the cytoplasm in an inactive form.  Upon ligand/estrogen binding, the ER is activated.  The ligand-ER complex migrates to the nucleus, where it is capable of binding with a specific DNA sequence on a target gene.  Subsequently, it activates the hormone response element, and initiates gene transcription.

Recently, science is discovering estrogen’s ability to have non-genomic effects.  G –protein coupled receptors, localized to the cellular membrane are activated by estrogen. Once activated, a cascade effect occurs to promote activation of the adenylyl cyclase/cAMP-dependent protein kinase A (PKA) pathway.  This is important as PKA signaling mediates anti-apoptotic effects, ensuring cell survival.  Once bound to estrogen, PKA can execute its various protective functions.  As mentioned above, estrogen is a rapid acting signal molecule that can phosphorylate existing proteins; as well as induce protein synthesis through gene transcription and translation.  Therefore, estrogen has both genomic and non-genomic effects.

 

PHYSICAL ACTIVITY REDUCES THE RISK OF CHRONIC DISEASES

Apart from the cardio protective and pathophysiological benefits of estrogen, physical inactivity is a significant predictor for developing T2D, CVD, and other metabolic/chronic disorders (5).  A sedentary lifestyle should be considered an important modifiable risk factor that the general population can manipulate.  As the exact exercise prescription is still a debate (intensity, frequency, and duration), researchers agree that physical activity provides benefits that outweigh any hormonal measurement.  Moderately intense physical activity (e.g., walking) reduces both CVD and T2D incidence rate, and decreases metabolic risk factors for developing CVD and T2D (5)(e.g., reduce blood pressure, decrease fat mass while improving/maintaining lean muscle mass(60), improve lipid profiles in patients with T2D, and improve insulin sensitivity(21)).

As the exact exercise prescription is still a debate (intensity, frequency, and duration), researchers agree that physical activity provides benefits that outweigh any hormonal measurement.

All the former are risk factors for CVD which can be counteracted through both vigorous and non vigorous activity.  For example, after 6 months of training, a low-volume moderate intensity group improved insulin sensitivity by 40%, whereas a high volume/high intensity group improved by 85% (29).  Therefore, epidemiological evidence reported in the literature shows that physical activity is inversely and causally related to the incidence of CVD.  Moreover, previous studies demonstrate that physical activity enhances whole body insulin sensitivity, resulting in enhanced muscle glucose uptake in both healthy and obese, insulin resistant animals and humans (31, 32, 33, 34).  It is important to note however, that exercise/physical activity not only is advantageous towards hormone concentrations, body mass, and macronutrient profiles, but is beneficial to the heart as well. This is through the up regulation of the inducible Hsp70 (50).

EXERCISE IS A FORM OF STRESS

This looks a bit stressful no?

WHAT?!  Exercise is a form of stress…this whole time health advocates have been saying it is a good tool to use for de-stressing the body and that it is good for you.  Well, yes as a matter of fact it does all of the latter, however, metabolically it is a form of stress.  That is why if someone is ill, or already has some type of physiological disorders (overtrained, adrenal fatigue, etc.) you would want to do low intensity, more parasympathetic dominant exercises so you are not putting your body into overdrive; exhausting and stressing the system.

An important function of the body is to maintain homeostasis in order for the organs, tissues, and systems to function optimally. This in turn results in fewer illnesses, and diseases, as these appear when the body is unable to maintain homeostasis in a certain localized area/vasculature.  Regardless of the benefits of physical activity, it causes the body to shift from a homeostatic state.  Moreover, muscles are being damaged, and depending on the intensity of exercise, metabolic accumulation can cause enzymes to not function optimally.  During exercise, the body’s ionic concentration changes, thereby affecting the sodium-potassium ATPase Pump.  There is also an increase in metabolites (e.g., lactate, adenosine diphosphate, inorganic phosphate, magnesium, and reactive oxygen species), and a decrease in the high energy metabolite, adenosine triphosphate.  All of this is accompanied by an elevated core temperature and oxidative damage.

Skeletal muscle adapts to this shift from homeostasis through the up regulation of heat shock proteins (HSP); which play an important role in cell maintenance and protein survival. The focus of this review will be on the inducible Hsp70, which received its name based on its molecular weight of 70-kD.  This increase in HSP has not only shown to be beneficial to the cardiovascular system, but to the musculoskeletal system as well.

However, there seems to be a sex difference both in the potential benefits of exercise and the up regulation of HSP.  For example, after performing short term (6 weeks) endurance training, females did not respond to continuous or interval training in terms of increasing HSP content.  However, males were able to increase HSP levels through both forms of training (45).  Therefore, it is evident that females may need to work at a greater intensity and/ or duration than their male counterparts, and may have a conflicting variable or hormone that inhibits this increase in HSP.

 

This is only part one, there is much more to this topic and I hope many of you readers are still with me.  Feel free to ask any questions if you need clarification in the comments section.  In part two, I will dig deeper in this cardio protective protein named Hsp70.

 

Strong-Athlete Contributor Nadine ShabanNadine Shaban

Nadine is a talented fitness model, trainer and nutrition expert who also holds a Masters Degree in Exercise Physiology from the University of Windsor. Her research specialty is glucose handling in Type 2 diabetics during high intensity interval exercise (HITT). Nadine also holds a B.S. in Kinesiology from the University of Windsor. In addition, Nadine is a certified strength coach under Charles Poliquin, a certified Biosignature Practitioner through Charles Poliquin, and a certified nutritional consultant through Precision Nutrition.

Nadine’s personal philosophy is to challenge people beyond what they believe they are capable of accomplishing. She hopes to inspire people to adapt to a healthier lifestyle. She believes people not only need to change their mindset towards exercise, but must also have a positive and balanced relationship with food. She truly believes a healthy mind represents a healthy body. For nutrition consultation or personal training, you can contact Nadine at nadineshaban@gmail.com.

 

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