LH, also known as lutropin is a hormone synthesized and secreted by gonadotropes in the anterior lobe of the pituitary gland. In concert with the other pituitary gonadotropin follicle stimulating hormone (FSH) it is necessary for proper reproductive function:
In the female, an acute rise of LH – the LH surge – triggers ovulation. FSH initiates follicular growth, specifically affecting granulosa cells. With the rise in estrogens, LH receptors are also expressed on the maturing follicle that produces an increasing amount of estradiol.
Eventually at the time of the maturation of the follicle, the estrogen rise leads via the hypothalamic interface to the “positive feed-back” effect, a release of LH over a 24-48 hour period. This 'LH surge' triggers ovulation hereby not only releasing the egg, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the endometrium for a possible implantation. LH is necessary to maintain luteal function for the first two weeks. In case of a pregnancy luteal function will be further maintained by the action of chorionic gonadotropin from the newly established pregnancy. LH supports thecal cells in the ovary that provide androgens and hormonal precursors for estradiol production.
In the male, where LH had also been called Interstitial Cell Stimulating Hormone, it stimulates Leydig cell production of testosterone.
LH acts upon the Leydig cell of the testis and is responsible for the production of testosterone, the “male hormone” that exerts both endocrine activity and intratesticular activity such as spermatogenesis.
Estradiol (17β-estradiol), on the other hand is a sex hormone. Mislabelled the "female" hormone, it is also present in males; it represents the major estrogen in humans. Estradiol has not only a critical impact on reproductive and sexual functioning, but also affects other organs including bone structure.
Estradiol, like other steroids, is derived from cholesterol. After side chain cleavage and utilizing the delta-5 pathway or the delta-4 pathway androstenedione is the key intermediary. Androstenedione is either converted to testosterone which in turn undergoes aromatization to estradiol, or, alternatively, androstenedione is aromatized to estrone which is converted to estradiol.
During the reproductive years, most estradiol in women is produced by the granulosa cells of the ovaries by the aromatization of androstenedione (produced in the theca folliculi cells) to estrone, followed by conversion of estrone to estradiol by 17β-hydroxysteroid reductase. Smaller amounts of estradiol are also produced by the adrenal cortex, and (in men), by the testes.
Estradiol is not only produced in the gonads: in both sexes, precursor hormones, specifically testosterone, are converted by aromatization to estradiol. In particular, fat cells are active to convert precursors to estradiol, and will continue to do so even after menopause. Estradiol is also produced in the brain and in arterial walls.
Estradiol enters cells freely and interacts with a cytoplasmic target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell.
Estradiol binds well to both estrogen receptors, ERα and ERβ, in contrast to certain other estrogens, notably medications that preferentially act on one of these receptors. These medications are called selective estrogen receptor modulators, or SERMs. Recently there has been speculation about a membrane estrogen receptor, ERX.
Functions of estradiol are diverse. In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the vagina, the cervical glands, the endometrium and the lining of the fallopian tubes. It enhances growth of the myometrium. Estradiol appears necessary to maintain oocytes in the ovary. During the menstrual cycle, estradiol that is produced by the growing follicle triggers, via a positive feedback system, the hypothalamic-pituitary events that lead to the luteinizing hormone surge, inducing ovulation. In the luteal phase estradiol, in conjunction with progesterone, prepares the endometrium for implantation. During pregnancy, estradiol increases due to placental production. In baboons, blocking of estrogen production leads to pregnancy loss suggesting that estradiol has a role in the maintenance of pregnancy. Research is investigating the role of estrogens in the process of initiation of labor.
The development of secondary sex characteristics in females is driven by estrogens, specifically estradiol. These changes are initiated at the time of puberty, most enhanced during the reproductive years, and become less pronounced with declining estradiol support after the menopause. Thus, estradiol enhances breast development, and is responsible for changes in the body shape affecting bones, joints, fat deposition. Fat structure and skin composition are modified by estradiol.
The effect of estradiol (and estrogens) upon male reproduction is complex. Estradiol is produced in the Sertoli cells of the testes. There is evidence that estradiol is to prevent apoptosis of male germ cells.
Several studies have noted that sperm counts have been declining in many parts of the world and it has been postulated that this may be related to estrogen exposure in the environment.
There is ample evidence that estradiol has a profound effect on bone. Individuals without estradiol (or other estrogens) will become tall and eunuchoid as epiphysieal closure is delayed or may not take place. Bone structure is affected resulting in early osteopenia and osteoporosis. Also, women past menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.
Estradiol has complex effects on the liver. It can lead to cholestasis. It affects the production of multiple proteins including lipoproteins, binding proteins, and proteins responsible for blood clotting.
Estrogens can be produced in the brain from steroid precursors. As antioxidants, they have been found to have neuroprotective function.
The positive and negative feedback loop of the menstrual cycle involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate gonadotropins.
Estrogen affects certain blood vessels. Improvement in arterial blood flow has been demonstrated in coronary arteries.
Estrogen is suspected to activate certain oncogenes, as it supports certain cancers, notably breast cancer and cancer of the uterine lining. In addition there are several benign gynecologic conditions that are dependent on estrogen such as endometriosis, leiomyomata uteri, and uterine bleeding.
The effect of estradiol, together with estrone and estriol, in pregnancy is less clear. They may promote uterine blood flow, myometrial growth, sitmulate breast growth and at term, promote cervical softening and expression of myometrial oxytocin receptors.
In the female, an acute rise of LH – the LH surge – triggers ovulation. FSH initiates follicular growth, specifically affecting granulosa cells. With the rise in estrogens, LH receptors are also expressed on the maturing follicle that produces an increasing amount of estradiol.
Eventually at the time of the maturation of the follicle, the estrogen rise leads via the hypothalamic interface to the “positive feed-back” effect, a release of LH over a 24-48 hour period. This 'LH surge' triggers ovulation hereby not only releasing the egg, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the endometrium for a possible implantation. LH is necessary to maintain luteal function for the first two weeks. In case of a pregnancy luteal function will be further maintained by the action of chorionic gonadotropin from the newly established pregnancy. LH supports thecal cells in the ovary that provide androgens and hormonal precursors for estradiol production.
In the male, where LH had also been called Interstitial Cell Stimulating Hormone, it stimulates Leydig cell production of testosterone.
LH acts upon the Leydig cell of the testis and is responsible for the production of testosterone, the “male hormone” that exerts both endocrine activity and intratesticular activity such as spermatogenesis.
Estradiol (17β-estradiol), on the other hand is a sex hormone. Mislabelled the "female" hormone, it is also present in males; it represents the major estrogen in humans. Estradiol has not only a critical impact on reproductive and sexual functioning, but also affects other organs including bone structure.
Estradiol, like other steroids, is derived from cholesterol. After side chain cleavage and utilizing the delta-5 pathway or the delta-4 pathway androstenedione is the key intermediary. Androstenedione is either converted to testosterone which in turn undergoes aromatization to estradiol, or, alternatively, androstenedione is aromatized to estrone which is converted to estradiol.
During the reproductive years, most estradiol in women is produced by the granulosa cells of the ovaries by the aromatization of androstenedione (produced in the theca folliculi cells) to estrone, followed by conversion of estrone to estradiol by 17β-hydroxysteroid reductase. Smaller amounts of estradiol are also produced by the adrenal cortex, and (in men), by the testes.
Estradiol is not only produced in the gonads: in both sexes, precursor hormones, specifically testosterone, are converted by aromatization to estradiol. In particular, fat cells are active to convert precursors to estradiol, and will continue to do so even after menopause. Estradiol is also produced in the brain and in arterial walls.
Estradiol enters cells freely and interacts with a cytoplasmic target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell.
Estradiol binds well to both estrogen receptors, ERα and ERβ, in contrast to certain other estrogens, notably medications that preferentially act on one of these receptors. These medications are called selective estrogen receptor modulators, or SERMs. Recently there has been speculation about a membrane estrogen receptor, ERX.
Functions of estradiol are diverse. In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the vagina, the cervical glands, the endometrium and the lining of the fallopian tubes. It enhances growth of the myometrium. Estradiol appears necessary to maintain oocytes in the ovary. During the menstrual cycle, estradiol that is produced by the growing follicle triggers, via a positive feedback system, the hypothalamic-pituitary events that lead to the luteinizing hormone surge, inducing ovulation. In the luteal phase estradiol, in conjunction with progesterone, prepares the endometrium for implantation. During pregnancy, estradiol increases due to placental production. In baboons, blocking of estrogen production leads to pregnancy loss suggesting that estradiol has a role in the maintenance of pregnancy. Research is investigating the role of estrogens in the process of initiation of labor.
The development of secondary sex characteristics in females is driven by estrogens, specifically estradiol. These changes are initiated at the time of puberty, most enhanced during the reproductive years, and become less pronounced with declining estradiol support after the menopause. Thus, estradiol enhances breast development, and is responsible for changes in the body shape affecting bones, joints, fat deposition. Fat structure and skin composition are modified by estradiol.
The effect of estradiol (and estrogens) upon male reproduction is complex. Estradiol is produced in the Sertoli cells of the testes. There is evidence that estradiol is to prevent apoptosis of male germ cells.
Several studies have noted that sperm counts have been declining in many parts of the world and it has been postulated that this may be related to estrogen exposure in the environment.
There is ample evidence that estradiol has a profound effect on bone. Individuals without estradiol (or other estrogens) will become tall and eunuchoid as epiphysieal closure is delayed or may not take place. Bone structure is affected resulting in early osteopenia and osteoporosis. Also, women past menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.
Estradiol has complex effects on the liver. It can lead to cholestasis. It affects the production of multiple proteins including lipoproteins, binding proteins, and proteins responsible for blood clotting.
Estrogens can be produced in the brain from steroid precursors. As antioxidants, they have been found to have neuroprotective function.
The positive and negative feedback loop of the menstrual cycle involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate gonadotropins.
Estrogen affects certain blood vessels. Improvement in arterial blood flow has been demonstrated in coronary arteries.
Estrogen is suspected to activate certain oncogenes, as it supports certain cancers, notably breast cancer and cancer of the uterine lining. In addition there are several benign gynecologic conditions that are dependent on estrogen such as endometriosis, leiomyomata uteri, and uterine bleeding.
The effect of estradiol, together with estrone and estriol, in pregnancy is less clear. They may promote uterine blood flow, myometrial growth, sitmulate breast growth and at term, promote cervical softening and expression of myometrial oxytocin receptors.