Steroid hormones are made from a 4-carbon ring and can be divided into five different classes: mineralocorticoids, glucocorticoids, androgens, oestrogens and progestogens. Although they exert their effects naturally within the body they can also be used in a therapeutic manner, such that treatment could result in a positive and desirable outcome. The following discussion shall provide an insight into some of the therapeutic benefits of each of class of steroid hormones.
Glucocorticoids and Mineralocortiocids:
Glucocorticoids and mineralocorticoids are produced by the adrenal glands. Cortisol is one of the most important glucocorticoid hormones in humans. Some important roles of cortisol include controlling blood glucose levels, raising fat levels through stimulation of appetite, defending the body against infection and responding to stress. Examples of stress include pain, fear, illness and changes in temperature. Cortisol deals with stress through mechanisms such as raising heart rate and increasing the blood supply to critical tissues.
Aldosterone is the main mineralocorticoid. It is responsible for increasing sodium re-absorption and the release of potassium and hydrogen ions from the body and so it controls water and salt balance. It exerts these effects at the collecting ducts of the kidneys. It also helps to maintain blood pressure. Therefore if levels of this hormone were to fall, salt and water balance would no longer be regulated and blood pressure would also fall.
Adrenal insufficiency is a condition whereby the production of mineralocorticoids and glucocorticoids is reduced. It presents itself in two forms. Primary insufficiency is due to the inability of the adrenal glands to produce enough of these steroid hormones (also known as Addisons disease when triggered by an autoimmune response) whereas secondary insufficiency is a result of poor stimulation of the adrenal glands. Symptoms include weakness, weight loss, extremely low blood pressure, dizziness, severe abdominal pain and craving for salty food due to loss of sodium. If the body is subjected to stress, as mentioned earlier, then it may respond with an adrenal crisis, which could result in death.
Fludrocortisone is a synthetic corticosteroid medication. The corticosteroid hormones are cortisol and aldosterone. It is used to treat conditions where there is insufficient production of these adrenal hormones and so is a form of hormone replacement therapy. Although it contains both cortisol and aldosterone it has much better mineralocorticoid potency. Therefore, it is often administered with hydrocortisone, a tablet replacing levels of cortisol in the body.
Fludrocortisone can also be used more specifically to treat salt-losing adrenogenital syndrome enabling the kidneys to preserve salt levels in the body as the reduction of aldosterone in the body causes high levels of salt to be lost in urine.
Synthetic glucocorticoids have other therapeutic effects. In relatively high concentrations cortisol can cause the lymph nodes to reduce in size and cause involution of the thymus. This leads to a decrease in the production of antibodies which may be necessary to prevent rejection of transplanted organs within the body.
They can also be used to treat inflammatory conditions such as asthma, rheumatoid arthritis and inflammatory bowel disease, as well as therapy for autoimmune diseases. Inflammation and immune reactions are caused by the action of multiple cytokines. It is thought that glucocorticoids prevent this production through inhibition of the multiple genes coding for proinflammatory cytokines. Further detail of the ways in which they work can be shown through a discussion of asthma, the most common inflammatory disease worldwide.
Glucocorticoids are the best form of treatment for asthma. These highly lipophilic steroids, which may be inhaled or taken orally, enter the airway cells and bind to cytosolic glucocorticoid receptors. This complex then moves to the nucleus where it alters levels of transcription of certain genes by binding to their glucocorticoid-responsive elements. It can also indirectly regulate expression of genes by interacting with other transcription factors. This eventually results in increased or decreased levels of protein. It increases transcription of genes that reduce inflammation such as lipocortin-1 in certain cells. It also raises production of interleukin receptor antagonists such as IL-1 receptor antagonist which blocks the binding of IL-1 to its receptor. This is beneficial as it is an inflammatory agent. It increases production of other interleukins such as IL-10 (an anti-inflammatory cytokine) and endopeptidases which break down inflammatory peptides. It can decrease transcription of genes that stimulate inflammation including various cytokines such as IL-2 and chemokines which attract inflammatory cells.
In addition to working at the molecular level in cells they directly hinder the action of macrophages, dendritic cells, airway epithelial cells, eosinophils and T-lymphocytes which promote inflammation. Glucocorticoids also prevent the release of mucus and plasma in the inflamed airways.
Testosterone is an important androgen hormone within males. It is vital for males to develop their sex organs and secondary sexual characteristics. Testosterone also has an effect on libido and sexual function. However with age, the levels of this steroid hormone gradually decrease. This condition is known as late-onset hypogonadism. Besides age, there are several other causes of low testosterone levels. Therefore males that lack testosterone or suffer from very low levels of the hormone can be treated through testosterone hormone replacement therapy. This helps to keep serum testosterone at expected levels.
This therapy can provide various benefits such as the restoration of secondary sexual characteristics and treat lack of libido and erectile function as well as increasing bone density and muscle strength. It has also been found to improve mood and raise energy levels while reducing feelings of anger, irritability and nervousness. The hormone may be taken orally, via intramuscular injections and transdermal systems.
Testosterone may also have benefits in women suffering from human immunodeficiency virus (HIV). Studies show that women suffering from HIV have low serum androgen levels which may be a cause of the wasting syndrome seen in them. It appears that providing them with testosterone may help to improve their weight and well-being.
Oestrogen and progestagens:
Oestrogens are the most important female sex hormones secreted by the ovaries. Estradiol is one of the main naturally occurring oestrogens. Progesterone is also produced by the ovaries and is an important progestagen in women. These two groups of hormone are extensively used in the production of contraceptives. The idea of contraception is appealing to many due to its ability to prevent unwanted pregnancies and its benefits are particularly appreciated in the USA where approximately 82% of all teenage pregnancies and 50% of all pregnancies are unplanned. There are various forms of contraceptive which shall now be discussed.
The oral contraceptive can be categorized into generations, each varying in the dose and type of hormones used. Each generation of contraceptives produced, was followed by a slightly modified and improved generation.
The first-generation combination birth control pill:
The steroid hormone progesterone is necessary for the contraceptive to work, however the costs of obtaining it and the difficulties associated with isolating it meant that alternative substances with similar activity had to be used instead. The derivative of androgen, ethisterone, fulfilled the requirements of progesterone and was easier to obtain. It was then modified and later termed norethindrone. It was most effective when produced in combination with a synthetic steroidal oestrogen, ethinyl estradiol, as well. Together these synthetic versions of progesterone and oestrogen helped to inhibit ovulation.
The levels of oestrogen were reduced in the second generation pills to reduce undesirable side effects such as coronary thrombosis. The third generation pills again had lowered levels of oestrogen and newer progestins.
Mechanism of action:
The dose of progestin administered in contraceptives suppresses Gonadotropin-releasing hormone (GnRH) and may also prevent the release of leutenising hormone (LH) from the pituitary gland. GnRH stimulates the production and release of LH and follicle stimulating hormone (FSH). As LH is necessary to trigger ovulation, the lack of it results in the inhibition of ovulation. Progestin also prevents penetration of the sperm in the egg through production of cervical mucus. It also prevents implantation of the fertilised egg should fertilization still occur.
Ethinyl estradiol works in a different way to progestins. It aids contraception by lowering the production of FSH, which aids follicular growth, from the pituitary. As a result, selection of a dominant follicle within the ovary is disallowed. Besides this it also up-regulates and prevents clearance of the progesterone receptor thereby increasing the effectiveness of the progestin. This method of contraception has a 99.9% success rate when used correctly.
Besides preventing unwanted pregnancies, it also helps to reduce iron deficiency through a reduced monthly blood loss and helps lower the risk of developing ovarian, endometrial and colorectal cancer.
Some women have a condition that increases their risk of developing problems when taking oestrogen. These include mothers who are breast-feeding and older women. As such, a progestin-only pill has been developed as well which contains a lower level of progestin than the combination pill. Therefore the ability of it to prevent ovulation is reduced. Instead there is more thickening of cervical mucus to lower the chances of sperm penetration and prevention of implantation of the embryo. On average, this pill has a slightly lower success rate of 99.5% when used correctly.
There are also long acting contraceptives which work through a gradual release of hormone allowing the contraceptive effects to be exhibited for longer periods. There are various forms such as injections into large muscles exerting its effects for up to four months, subdermal implants lasting up to five years, transdermal patches, intrauterine devices and vaginal rings. These contraceptives are similar to the pill as they too can contain a combination or progestin-only hormones.
Emergency contraception is also available in case contraception has failed or not been used and an egg has been fertilized. This prevents implantation by altering the endometrium. Similar to the oral contraceptives mentioned earlier it may be a combination or progestin-only pill. The chances of becoming pregnant, is reduced on average by 75%, if taken as soon as unprotected intercourse has occurred.
The beneficial uses of steroid hormones has led to their wide spread use to treat diseases and various other conditions. With further research it may be possible in future to find even more therapeutic effects of steroid hormones to benefit mankind.
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