Receptor Site Disorders and Adrenal Fatigue Syndrome

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM

An illustration of a receptor siteReceptors sites are proteins that can be found on the surface of each cell. Think of them as ears, listening to the messenger molecules that surround each cell. These chemical messengers (hormones and transmitters) tell the receptors what to do and how to respond to the needs of the body. Although many people are unfamiliar with what a receptor site is, and chances are they’ve never heard of them, they hold a very fundamental role in our body. A malfunctioning or damaged receptor site can cause havoc in your body. Without properly functioning receptors, essential biochemical reactions and assimilation will not be successful.

Receptor Site 101

There are two t???? ?f r????t?r?: ?nt?rn?l receptors ?nd ??ll-?urfa?? r????t?r?
A description of each will be discussed below.

Int?rn?l r????t?r?, ?l?? known ?? ?ntr???llul?r or ??t??l??m?? receptors, are f?und in th? ??t??l??m ?f th? ??ll ?nd r????nd to hydrophobic ligand m?l??ul?? th?t ?r? ?bl? to travel ??r??? the ?l??m? membrane. Once inside the ??ll, m?n? of these molecules bind to ?r?t??n? th?t ??t as regulators ?f mRNA ??nth???? t? m?d??t? gene expression. Gene expression is th? cellular process ?f transforming th? information in a ??ll’? DNA into a ???u?n?? of ?m?n? ???d? that ultimately f?rm? a ?r?t??n. When the l?g?nd binds to an ?nt?rn?l receptor, a ??nf?rm?t??n?l ?h?ng? ?x????? a DNA-b?nd?ng ??t? ?n th? ?r?t??n. Th? l?g?nd-r????t?r ??m?l?x m?v?? into th? nu?l?u?, b?nd? t? specific regulatory r?g??n? of the chromosomal DNA, ?nd ?r?m?t?? the ?n?t??t??n ?f tr?n??r??t??n. Int?rn?l receptors ??n d?r??tl? influence g?n? ?x?r?????n without having t? pass the signal ?n t? an?th?r r????t?r ?ite ?r its messengers.

Cell-surface receptors, ?l?? kn?wn as tr?n?m?mbr?n? r????t?r?, ?r? ??ll ?urf???, m?mbr?n?-?n?h?r?d, or integral proteins that bind t? ?xt?rn?l l?g?nd m?l??ul??. Th?? t??? ?f receptor spans the ?l??m? m?mbr?n? ?nd ??rf?rm? signal tr?n?du?t??n, converting ?n ?xtr???llul?r ??gn?l ?nt? ?n intracellular ??gn?l. L?g?nd? that ?nt?r??t with ??ll-?urf??? r????t?r? do n?t have to enter th? ??ll th?t they affect. Cell-surface r????t?r? ?r? ?l?? ??ll?d ??ll-?????f?? proteins ?r m?rk?r? b???u?? they ?r? ?????f?? to individual ??ll t????.

E??h ??ll-?urf??? r????t?r has three m??n ??m??n?nt?: an external l?g?nd-b?nd?ng domain (?xtr???llul?r d?m??n), a h?dr??h?b?? m?mbr?n?-???nn?ng region, and an ?ntr???llul?r d?m??n inside th? ??ll. The size and ?xt?nt ?f each ?f th??? d?m??n? v?r? widely, d???nd?ng ?n th? t??? of r????t?r.

C?ll-?urf??? receptors are ?nv?lv?d in m??t ?f th? signaling in mult???llul?r ?rg?n??m?. There are three g?n?r?l ??t?g?r??? ?f ??ll-?urf??? receptors: ??n ?h?nn?l-l?nk?d r????t?r?, G-protein-linked r????t?r?, ?nd enzyme-linked receptors.

S?n??r? r????t?r? can be classified b? the type ?f ?t?mulu? th?t generates a response in th? r????t?r. Br??dl?, sensory r????t?r? r????nd to ?n? ?f four primary ?t?mul?:

  • Chemicals (?h?m?r????t?r?)
  • T?m??r?tur? (thermoreceptors)
  • Pr???ur? (mechanoreceptors)
  • L?ght (?h?t?r????t?r?)

All sensory receptors r?l? ?n ?n? ?f th??? f?ur ??????t??? t? d?t??t ?h?ng?? in the ?nv?r?nm?nt, but m?? b? tun?d t? d?t??t ?????f?? ?h?r??t?r??t??? ?f each to ??rf?rm a ?????f?? ??n??r? fun?t??n. In some ?????, th? m??h?n??m of action for a r????t?r ?? n?t ?l??r. F?r ?x?m?l?, h?gr?r????t?r? that r????nd to ?h?ng?? ?n hum?d?t? ?nd ??m?r????t?r? th?t r????nd to th? ??m?l?r?t? of fluids may d? so v?? a mechanosensory mechanism ?r may detect a chemical ?h?r??t?r??t?? of th? environment.

Receptor site, light, and intensityS?n??r? receptors perform ??untl??? fun?t??n? in ?ur bodies. Concerning our v????n, r?d and ??n? ?h?t?r????t?r? respond t? l?ght ?nt?n??t? and ??l?r. Dur?ng h??r?ng, m??h?n?r????t?r? ?n hair ??ll? ?f th? ?nn?r ??r detect vibrations ??ndu?t?d from th? ??rdrum. Dur?ng t??t?, sensory n?ur?n? in our taste buds d?t??t chemical ?u?l?t??? ?f ?ur f??d? ?n?lud?ng ?w??tn???, bitterness, ??urn???, ??lt?n???, and um?m? (savory taste). During smell, ?lf??t?r? receptors r???gn?z? m?l??ul?r f??tur?? of wafting odors. Dur?ng t?u?h, mechanoreceptors in the ?k?n ?nd other tissues r????nd t? variations ?n pressure.

The adrenergic r????t?r? (or ?dr?n????t?r?) are a ?l??? ?f m?t?b?tr???? G ?r?t??n-??u?l?d r????t?r? that are t?rg?t? ?f the ??t??h?l?m?n??, ???????ll? n?r???n??hr?n? ?r n?r?dr?n?l?n?, ?nd epinephrine (?dr?n?l?n?). Alth?ugh dopamine ?? a catecholamine, ?t? r????t?r? are in a d?ff?r?nt category.

M?n? ??ll? ??????? th??? types of receptors, and the b?nd?ng ?f an ?g?n??t will g?n?r?ll? cause a ??m??th?t?? (or sympathomimetic) r????n?? (?.g., th? f?ght-?r-fl?ght r????n??). For instance, th? h??rt r?t? will ?n?r????, ?u??l? will d?l?t?, ?n?rg? will b? mobilized, ?nd bl??d flow w?ll b? d?v?rt?d fr?m n?n-????nt??l ?rg?n? t? skeletal mu??l?.

Th?r? ?r? tw? m??n groups of adrenergic r????t?r?, a ?nd ß, w?th ??v?r?l ?ubt????. a r????t?r? h?v? th? ?ubt???? a1 (? Gq ??u?l?d r????t?r) ?nd a2 (? G? ??u?l?d r????t?r). Phenylephrine ?? a ??l??t?v? ?g?n??t of th? a r????t?r.

Adr?n?l?n? (???n??hr?n?) r???t? w?th b?th a- and ß-?dr?n????t?r?, ??u??ng vasoconstriction and v???d?l?t??n, r?????t?v?l?. Alth?ugh a receptors ?r? l??? ??n??t?v? t? epinephrine, wh?n ??t?v?t?d, they override the vasodilation m?d??t?d by ß-adrenoceptors. Th? result is th?t high l?v?l? of ??r?ul?t?ng ???n??hr?n? cause vasoconstriction. At lower l?v?l? ?f ??r?ul?t?ng ???n??hr?n?, ß-?dr?n????t?r stimulation d?m?n?t??, ?r?du??ng ?n overall v???d?l?t??n. Because blood pressure is such an important component of optimum health, the body has other mechanisms in place to concurrently monitor and regulate elasticity of the blood vessel. Nitric oxide, a gas that is released in the endothelial wall, for example, causes vasodilation.

Receptors and Adrenal Fatigue

Adrenal fatigue, in its advanced stages, is often associated with sympathetic overtone. The body is often flooded in a sea of adrenaline as the body’s last resort to overcome stress. On? ?m??rt?nt th?ng to n?t? ?b?ut ?dr?n?l f?t?gu? is th?t th? m?r? ?t ?r?gr?????, ?dr?n?l?n? l?v?ls tend to be normal or high, many ?r?bl?m? which d?dn’t ?x??t before, begin t? ?h?w u?, such as anxiety, dizziness, panic attack, heart palpitations, etc. M?r??v?r, th? ??m?t?m? ?r? ?? g?n?r?l th?t th?? ?r? v?r? d?ff??ult t? d??l w?th. Receptor sites may be damaged with prolonged overstimulation, leading to hypers?n??t?v?t? t? r???t??n? ?nd r???t??n? t? ?th?r ?xt?rn?l f??t?r? ?u?h ?? medications, ??llut?d ?nv?r?nm?nt, ?nd ?h?m???l?.

Paradoxical reactions are commonly reported for no apparent reason. N?rm?ll?, th??? ????l? wh?n ?n a n?rm?l ?nv?r?nm?nt, w?n’t ?x??r??n?? this, but wh?n th?? ?x??r??n?? ?r ?r? sufferers ?f adrenal f?t?gu?, th?? begin t? h?v? ??n??t?v?t? ???u??. All th? r????n? f?r ?u?h ??m?t?m? ?r? n?t kn?wn, and laboratory test are not sophisticated enough to help in the assessment. It is clear, however, upon detailed history, that receptors are probably involved by exclusion. Such r????t?r ??t? d??fun?t??n wh??h m?ght b? t??d ?nt? l?v?r ??ng??t??n, ?nt? ?xtr???llul?r m?tr?x ??llut??n, ?? w?ll m?t??h?ndr??l d???????, could ??ntr?but? t? th??? ??m?t?m?. The clinical picture is convoluted, and clinicians are often misled into looking for a needle in a haystack, such as genetic testing for MTHFR or pyroluria, for these anomalies. Sometimes genetic testing may add to the confusion because the results can be mistaken as the “smoking gun” – when in reality they are simply concurrent events that are coincidental.

Receptor Sites and Adr?n?l F?t?gu? S?ndr?m?

Adrenal fatigue and the receptor siteAdr?n?l F?t?gu? S?ndr?m? (AFS) ?? ?u?t? ??mm?n n?w ?m?ng m?n ?nd w?m?n wh? ?r? ?uff?r?ng from d??l? ?tr???. Th?? ?? a clinical ??nd?t??n wh?n th? ?dr?n?l gl?nd? function is sub optimum, but laboratory test remains normal. Th? adrenal glands ?r? l???t?d ?b?v? th? k?dn??? ?nd ???r?t? th? cortisol hormone, which ?? th? m??n h?rm?n? h?l?ing u? h?ndl? ?tr???ful ??tu?t??n?.

Th? ?dr?n?l gl?nd? ??n b? ?v?rw?rk?d; wh?n a ??r??n ?x??r??n??? stress, ??rt???l m?? b???m? depleted ?n?? th? ?dr?n?l? ??n n? l?ng?r handle the d?m?nd? ?n ?t.

As adrenal fatigue progresses from mild to advanced stages, n?t????bl? d??r???? ?n ?n?rg?, d?g??t??n ?r?bl?m?, ?rr?t?bl? b?w?l syndrome ?nd ?n ?v?r?ll ?n?b?l?t? t? h?ndl? ?tr??? ?r? ju?t ??m? ?f th? ?n?t??l ??m?t?m? ?f ?dr?n?l f?t?gu?. Since adr?n?l fatigue is clinically presented as a continuum, symptoms v?r??? ????rd?ng t? ?t?g?s. th? more advance the ?t?g? ?n wh??h ??m??n? ?? in ?r ?? ?x??r??n??ng, th? w??k?r ?nd th? fr?g?l? th? b?d? w?ll b? ?nd ?? a result, th? b?d? will not b? ?bl? t? ?l??r ???umul?t?ng m?t?b?l?t?? on a timely basis. C?n???u?ntl?, th?r? is often ?n increase ?n th? b?d?’? toxic m?t?b?l?? by-product l??d. Such metabolites are inflammatory in nature, wh??h ?ft?n w?ll lead to increase in asynchronous v?br?tory effort. Thu?, wh?n ?tr??? n?w ??m?? ?l?ng??d? w?th ??m? ?f th??? other factors like b??n ?x????d t? ?h?m???l? ?u?h as: perfumes, g???l?n?, ?ndu?tr??l w??t?, l?ght?ng, ?nd fluorescent l?ght?, all these ??mb?n?d ??n’t tr?gg?r ?n?th?ng ?n a n?rm?l ??r??n. On th? ??ntr?r?, th??? factors w?ll ?m?l?f? th? r????n?? ?n a ??r??n w?th adrenal f?t?gu?. In ?dd?t??n, ?ll th??? ??m?l??n? ?u?h ?? ?u?h ?? fatigue, br??n f?g, ?nx??t?, ?h?rtn??? ?f br??th ?nd v?r? unu?u?l r????n??? t? f??d, ?h?m???l ??n??t?v?t???, ?r? ??mm?n n?w?d??? ?n th? ?????t?. Receptor site insult becomes a potential aggravating factor to the already convoluted and complex clinical picture of decompensation.

Thu?, receptor site ?r?bl?m ?? ?n? ?f th? m?j?r ??n??rn?, but th?r? ?? mu?h m?r? th?n th?t. There ?r? a f?w th?ng? wh??h n??d t? b? ??n??d?r?d ?u?h ?? t?k?ng a ?t?? b??k and ??tu?ll? ?d?nt?f??ng th? ??u?? ?f th? ?r?bl?m, ?nd ?t ?? ?m??rt?nt t? n?t? th?t ?n?? ??u h?v? ?dr?n?l f?t?gu?, the b?d? ?lr??d? ?? weaker th?n b?f?r?. Wh?n th? b?d? ?? w??k, ?t ?? not ?bl? t? ?ssimilate v?t?m?n? ?ff??t?v?l?, ?? br?ng?ng ?n m?r? ?r?bl?m?, or ?dd?ng m?r? burd?n unt? ??ur metabolic load. Many in such state cannot take vitamins or minerals. They can make you worse.

Understanding the role receptor site dysfunction plays in adrenal fatigue therefore is important in order to formulate a successful recovery plan naturally.

Healing a Receptor Site

Fortunately, a receptor site does regenerate over time as the body has self healing mechanisms in place if damage is not too severe. Unfortunately, the process is slow and tedious. Consider the following:

  • Avoiding additional insults without depriving the body of nutrients is key. This is a process requiring much clinical skills and trial and error even in the best of hands. Even good nutrients can be damaging, so they need to be isolated by clinical challenges. Once identified, they need to be removed.
  • Replenishment with alternative nutrients that are not receptor site toxic can be considered. Oftentimes, it comes down to dosage and delivery system, since the same compound in different doses can have different clinical effects. For example, 1000 mg of vitamin C may be unnecessary, but taking 50 mg may be what is needed.

Perfumes and receptor site

  • Avoid a toxic external environment should be considered. Stay away from petrochemical products that can be toxic to a receptor site. For example, refrain from perfume use or exposure to gasoline and smoke.
  • Keep your body well hydrated with proper electrolyte balance in order to keep extracellular matrix pollution to a minimum
  • Keep liver function optimized to reduce accumulation of toxic metabolic load. Avoid aggressive detoxification to prevent adrenal crashes.
  • Avoid inflammatory foods such as hydrogenated fat that can be toxic to the receptor site.
  • Avoid stress to reduce adrenaline load. Adrenal breathing exercises can be very helpful.

The above need to be all deployed concurrently to effectively help the body recover. The process is slow and much patience is required. Since receptor site dysfunction in a clinical setting is largely arrived by exclusion when all other investigative and clinical trials have failed and laboratory test are unhelpful. By the time this is considered, sufferers are already weak, fragile, sensitive, and fragile. Hard science are still decades away as most research currently occurs in the laboratory only. Modalities that are natural without any harm to the body should not be deprived of trial. Consulting an experienced clinician is key. Efforts to self-navigate often fail and can worsen adrenal fatigue.

© Copyright 2017 Michael Lam, M.D. All Rights Reserved.

An illustration of a receptor site


  • Judy says:

    I was very sick for several years with all the adrenal fatigue symptoms and very high cortisol levels taken 5 times over 1 1/2 years and there was no one to help me or who believed me. I had severe itching all the time and through my own efforts and a Dr. way out of state found I have Mast Cell Activation. I started bio identical hormones and my cortisol returned to normal and I am enormously better. I have a regimen of deep breathing, meditation music, acupuncture, supplements and know when anxiety is ramping up after a lot of stress. I have been a long time reader of Dr. Lam’s books and publications and he is the one who pointed me towards adrenal fatigue. I am grateful to Dr.’s like him who can help us.

  • Dale Miller says:

    “Consult your medical clinician” is about the worst advice I have ever heard. After many years of diligently chasing these health problems, I have not been impressed with the medical help I have received.

  • Jennifer Robinson says:

    Self-help is sometimes all one has. I have had no luck finding a clinician who understands any of this. Most believe adrenal fatigue is imaginary and prescribe antidepressants. What on earth is one to do?

  • Barbara says:

    This is the most complete, accurate and sensible explanation of why my body reacts so erratically to such a multiplex of stimuli I have read anywhere in my extensive web research. As a lay person trying to help myself — because physicians and even natural healers only offer their specific tools aI alreadynd not the holistic approach — such information is KEY to self-help. You have helped me to understand the process a little more so that I don’t feel like all I can do is stumble around in the desert of my symptoms and hope for the best. Since I already practice a very highly informed program (well-researched diet, supplements, lifestyle) but symptoms still persist, I don’t know what more to do. Do you have a health clinic or onsite program I can enter?

    • Dr.Lam says:

      We have a telephone coaching service that you can enter if you qualify. You can call my office for more details.