Introduction to Hormones

Georgina Grimsey

Nov 21, 2019

Hormones

Hormones are signalling molecules secreted by glands
(endocrine signalling system) for communication between organs and tissues for
physiological regulation and behaviour. They affect their target cells by
binding to a specific receptor to activate a signal transduction pathway. Upon
secretion, certain hormones are water-soluble and are readily transported
through the circulatory system, while others are lipid-soluble and need
transportation through carrier plasma glycoproteins. And prohormones need to
undergo regulated maturation processes before it can be active.

Due to the large diversity of cellular and bodily processes
controlled by hormones, there are also various disorders related to defective
endocrine functions. Levels of hormones therefore reflect the status of
physiology and may indicate disease. Measurements of serum TSH are most often
used to diagnose and manage thyroid disorders, HCG is generally used to confirm
pregnancy, LH levels indicate timing of ovulation, FSH levels can be used to
investigate female infertility, or ovarian and testicular anomalies, and the
Alpha Unit is the subunit in common between TSH, HCG, LH and FSH. Increased or
decreased SHBG levels have various diagnostic implications, Progesterone levels
are often monitored during high-risk pregnancies, high PRL levels may be
related to pituitary or other PRL-releasing tumours, T4 levels are critical for
foetus and child development, while its precursor thyroglobulin is a potential biomarker
for iodine deficiency. Finally, GH testing is mainly used for identifying
growth hormone deficiency.

Human Chorionic Gonadotropin (HCG)

Human Chorionic Gonadotropin is a glycoprotein hormone
essential for the maintenance of pregnancy. The embryonic trophoblast cells of
the placenta are mainly responsible for the secretion of this hormone, thus
making HCG the globally used pregnancy marker. Both its subunits are
glycosylated in variable ways and the measurement of HCG, or its different
molecular forms, can be utilized for various clinical purposes, for example,
certain forms are diagnostic for pregnancy-related disorders, or for
trophoblastic tumours.

Thyroid-Stimulating Hormone (TSH)

Thyroid-Stimulating Hormone (a.k.a Thyrotropin) is a
glycoprotein hormone secreted by the anterior pituitary gland. It activates the
thyroid gland to secrete T4 (to convert to T3 in the liver), thus being a key
regulator of normal development and metabolism. 
The levels of T3 and T4 inversely feedback to the levels of TSH. Thus,
serum TSH levels are measured to diagnose and manage thyroid disorders. It is
important for clinical applications to recognize that TSH levels are subject to
circadian and ultradian rhythms.

Luteinizing Hormone (LH)

Human Luteinizing Hormone (a.k.a. Lutropin), is a
glycoprotein hormone secreted by the anterior pituitary gland. This hormone is
a key regulator for ovulation, and it stimulates testosterone production by the
Leydig cells of the testis. The clinical indications of assaying LH levels in
blood or urine include predicting the timing of ovulation, investigating
menstrual irregularities, and diagnosing early or delayed puberty. The LH test
is often used in conjunction with other hormonal tests, such as tests for FSH
or TSH levels.

Follicle-Stimulating Hormone (FSH)

Follicle-Stimulating Hormone is a glycoprotein hormone
secreted from the anterior pituitary gland. FSH serves as a ligand to activate its
receptor FSHR, which is expressed mainly by ovarian granulosa cells and
testicular Sertoli cells, but also by osteoclasts and certain tumour cells. In
males, FSH ensures normal testes development and it maintains normal
spermatogenesis and Sertoli cell activities important for continued male
fertility. In females, FSH drives follicle growth and granulosa cell
proliferation and oestrogen production. 
Serum or urine FSH levels can be measured to investigate female
infertility, menstrual irregularities, or to diagnose conditions related to
ovarian or testicular dysfunction. FSH tests are often carried out together
with an LH test.

Alpha Subunit

All four above-mentioned hormones (HCG, TSH, LH, and FSH) belong
to the gonadotropins, glycoprotein hormones having the same Alpha subunit in
common. The Alpha subunit is required for the biological activity of these
hormones. Anti-human alpha subunit specific antibodies are recommended only as
detection antibodies, with human glycoprotein hormone (hCG, LH, FSH and TSH)
beta subunit specific antibodies to use as capture antibodies.

Sex Hormone-Binding Globulin (SHBG)

Sex hormone binding globulin (SHBG) is a steroid-binding
serum glycoprotein synthesized in the liver. Synthesized SHBG is secreted into
the circulation, where it binds the sex hormones testosterone and oestradiol
with high affinity and specificity. (Other steroid hormones such as progesterone,
cortisol, and other corticosteroids are bound by Transcortin). Thus, SHBG
regulates sex hormone bioavailability (only free steroids are active) by
inhibiting their function.

SHBG immunoassays are often used to assess patient
testosterone status, such as in male infertility treatment or female hirsutism.
In addition, conditions like diabetes, hypothyroidism, or polycystic ovary
syndrome are indicated by low SHBG plasma levels, while its levels are high
with pregnancy, hyperthyroidism or anorexia nervosa.

Progesteron (PR)

The steroid hormone PR
is produced in the corpus luteum after ovulation and in the placenta during
pregnancy. As the “pregnancy hormone” it converts the endometrium to its
secretory stage to prepare the uterus for implantation, it makes the immune
system to tolerate the pregnancy, it reduces uterine contractibility, and it
inhibits lactation and labour until birth. When there is no pregnancy,
gradually reduced PR levels will ultimately trigger menstruation. In early
pregnancy, progesterone levels, in addition to HCG levels, are monitored for
more precise diagnosis of an ectopic or otherwise dysfunctional pregnancy. As
low progesterone levels can lead to pregnancy termination, progesterone levels
are often monitored during high-risk pregnancies to evaluate and ensure foetal
health.

Prolactin (PRL)

Prolactin is a peptide
hormone secreted primarily by the lactotroph cells of the pituitary gland.
During pregnancy, PRL acts in concert with other hormones, including progesterone
and insulin, to promote mammary gland growth and development. In the postpartum
period, PRL stimulates lactation. It also reduces Gonadotropin-Releasing
Hormone, thus supressing LH and FSH and inhibiting ovulation. High PRL levels
are expected during pregnancy and nursing. And in other situations, it may
indicate a potential disorder, may be related to pituitary or other
PRL-releasing tumours, certain kidney or liver diseases, or hypothalamus
diseases. PRL levels are often measured in cases of infertility or irregular
menstrual periods, or testicular dysfunction. PRL levels vary naturally during
the day, which needs to be considered during diagnostic use.

Thyroglobulin

Thyroglobulin is the
predominant protein produced by the thyroid gland. This glycoprotein is the
precursor of thyroid hormones tri-iodothyroxine (T3) and thyroxine (T4). In
addition, it serves as a storage protein for iodide that ensures sufficiency of
this essential element. Thus, the Thyroglobulin levels may serve as a marker for
Iodine deficiency. Thyroglobulin is also produced by thyroid cancer, and its
levels are commonly used to monitor the treatment of cancer patients who have
undergone thyroidectomy. Because Thyroglobulin is also produced by normal
thyroid gland, it is not suitable as a diagnostic cancer biomarker. Blood
thyroglobulin levels can also be elevated in some cases of Grave’s disease.

Thyroxine (T4)

The thyroid gland
produces the tyrosine-based hormone Thyroxine, also called T4 for its four
iodine moieties from its precursor Thyroglobulin. T4 levels are in high
abundance in the blood, but only after a de-ionidation step (to become T3) its
potency becomes 3-4 times higher as a hormone. This conversion can happen
either in the thyroid gland or in the target cells. The levels of T4 are 14-20
times higher than T3 levels, thus the metabolism of carbohydrates, lipids and
proteins is regulated by the fine-tuning of T3 levels.

Both T3 and T4 act
together with its precursor Thyroglobulin as Iodine reservoir in the Thyroid,
and Iodine deficiency leads to increase T4 levels and increased size of the
thyroid gland. In the foetus and during childhood, thyroid hormones are
critical for functions such as brain development, neuronal differentiation, and
formation of neural processes.

Growth Hormone (GH)

Human growth hormone (GH) is a peptide hormone secreted by
the anterior pituitary gland. GH stimulates various processes related mostly to
growth and regeneration. Besides stimulating longitudinal bone growth, GH
regulates cell growth and differentiation, as well as metabolic processes in
various tissues. GH testing is mainly used for identifying growth hormone
deficiency or, less commonly, excess GH related to acromegaly and gigantism.

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