The relationship between histamine, oestrogen, progesterone, and cortisol

The health status of the female reproductive cycle is a reflection of both local and systemic health. The wide range of signs, symptoms and disorders that can occur as a result of an imbalanced cycle can present as reproductive or non- reproductive issues. The synergistic nature of systemic functionality in the body is demonstrated by the interaction between histamine, oestrogen, progesterone, and cortisol. This article reviews the current evidence regarding histamine metabolism and the mechanistic and functional links between histamine, oestrogen and progesterone.

Histamine is a pleiotropic biogenic amine required for the normal function of many processes in the body including inflammation, immunity, neuromodulation, and gastric acid secretion.¹ Normally, the formation, storage, utilisation, and breakdown of histamine is tightly controlled by several measures due to its capacity to stimulate significant biological effects. However, the integrity of such measures can be adversely influenced by a number of endogenous and exogenous factors.¹

In the cellular organelle, the Golgi apparatus, histamine is synthesised by the decarboxylation (removal of a carbon atom) of L-histidine, a process catalysed by the inducible enzyme histidine decarboxylase (HDC).^1,3 HDC is present in mast cells and basophils (which store histamine) and enterochromaffin- like, histaminergic neurons, lymphocytes, monocytes, platelets, neutrophils, gastric, and dendritic cells, which produce histamine in response to specific stimulus (as opposed to storing it).^1-4

One of the steps that determines the biological effect of histamine is its binding to its receptors (H1-4), with each receptor-type varying in binding capacity, physiological location and the processes consequentially induced.^3,5

The H1 receptor is expressed on smooth muscle tissue, vascular endothelial cells, and the brain.⁶ It is involved in immune- (IgE) and inflammatory-mediated processes initially due to the activation of this receptor. The classic histamine-associated effects include vasodilation, erythema, and oedema, as well as symptoms such as allergic rhinitis, dermatitis, urticaria, asthma, and anaphylaxis.^3,4 H1 also mediates adrenal catecholamine- release and central nervous system (CNS) neurotransmission.⁶

The H2 receptor is located on immune, gastric mucosal, brain, adipocyte, vascular, and uterine smooth muscle cells.
Its activation is involved in the regulation of gastric acid secretion, gastrointestinal motility, and cell growth and differentiation.^4,6 

The H3 receptor has a significant presence on CNS histaminergic neurons, eosinophils, dendritic cells and monocytes. It regulates the secretion of neurotransmitters, nerve supply to the heart and blood vessels and smooth muscle contraction.⁶ 

Lastly, the H4 receptor is mainly expressed on haematopoietic cells, as well as on various immune cells (i.e. mast cells, eosinophils, T cells, basophils, and monocytes), keratinocytes, and dendritic cells. Its activation is thought to be involved in inflammation and allergic processes.^4,6 

Another internal measure that influences histamine’s biological effects is its stimuli-induced release by either immune- or non- immunological processes. 

Immune-mediated (‘classic’) histamine release involves mast cells and basophils, which degranulate stored histamine after antigen-induced IgE antibodies bind to membrane receptors.^5,7 

Non-immunological histamine release involves the degranulation of stored histamine from mast cells and basophils or the passive transport of histamine in non-storing cells, which can be induced by endogenous (neuropeptides, cytokines, complement) or exogenous (alcohol, food, medication) factors.