07-03-2010, 02:12 PM
Prolactin
September 1 2006 at 2:21 PM chocogirl (Login chocogirl)
SENIOR MEMBER
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Breast changes during physiological hormonal fluctuations influencing the actions of prolactin
Puberty
The major influence on breast growth during puberty is estrogen, which acts by the development of prolactin-dependent estrogen receptors. In most women the first response to rising estrogen levels is an increase in size, pigmentation of the areola, and the formation of abreast mass beneath the areola (thelarche). The primary effect of estrogen is to stimulate growth in the ductal portion of the gland. This growth can begin at any age between 8 to 14 years and normally occurs in a span of four years. Normal development requires prolactin,estrogen, progesterone, growth hormone, insulin, cortisol, thyroid and parathyroid hormone,and growth factors; but this growth is only in anticipation of the development of the fully functional status characterized by full development of the alveoli which occurs only during pregnancy.
Premature thelarche is characterized by the nonprogressive nature and absence of other secondary sexual characteristics. Confirmation is obtained by a normal FSH, LH, prepubertal estrogen concentration, immature vaginal maturation index, and a negative ultrasound exam to rule out ovarian pathology. If other secondary sexual characteristics are noted, a hand film for bone age and a GnRH stimulation test are performed to document precocious puberty.
Cyclic changes in estrogen/progesterone during the normal menstrual cycle result in continued development of breast structures. As estrogen and progesterone levels fall near the end of the cycle, prolactin-induced secretory changes become evident in the alveolar lumen during the first few days of the menses. The breasts are largest in this phase and are smallest on days 4to 7 of the cycle, which is the ideal time for breast self-exam.
Pregnancy
Differentiation of the breast to its mature functional status occurs by the third month of pregnancy. The true glandular acini (true alveoli) develop under the influence of prolactin,human placental lactogen, estradiol, progesterone, insulin, cortisol, growth hormone, IGF-1,and EGF. Thyroid hormones also promote alveolar growth of the glands.
Pregnancy provides a unique opportunity to evaluate the facilitator and inhibitory actions of various hormones; specifically, the interactions of prolactin, estradiol, and progesterone on the development of the lactating breast.
In humans, prolactin acts to (1) increase arginase activity, (2) stimulate ornithine decarboxylase activity, and (3) enhance the rate of transport of polyamines into the mammary gland. All result in increased spermine and spermidine synthesis (polyamines) which are required for milk production. The polyamines stabilize membrane structures, increase transcriptional and translational activities, and regulate enzymes. Prolactin in cultured mammary gland explants also elicits increased messages and synthesis of casein, spermidine,lactose, and phospholipids which are all required for lactation. Estradiol levels, rising throughout pregnancy, act at the hypothalamic level to increase prolactin secretion.
Progesterone interferes with prolactin action at the alveolar cell's prolactin receptor level. While estrogen and progesterone are required to get full activity of the prolactin receptor,progesterone antagonizes the positive action of prolactin on its receptor by (1) inhibiting up regulation of the prolactin receptor, (2) reducing estrogen binding (lactogenic activity), and (3)competing for binding at the glucocorticoid receptor.
Actual lactation occurs after birth by allowing prolonged prolactin elevation without progesterone inhibition because of the more rapid clearance of progesterone in contrast to prolactin. It takes approximately seven days for prolactin to reach non-pregnant levels, while estrogen and progesterone elevations are cleared in three to four days postpartum.
In the first week postpartum, prolactin levels decline 50% (to about 100 ng/ml). Suckling results in increased prolactin, which is important in the initiation of lactation. Until approximately two to three months postpartum, basal levels are 40 to 50 ng/ml in the lactating female, and there are large (10 to 20-fold) increases with suckling. Basal prolactin levels remain normal or slightly elevated with a twofold increase with suckling in the third to sixth months postpartum. Increased prolactin levels are required for lactogenesis; however,nonpregnant levels are adequate to maintain lactation.
Progesterone, while still present postpartum, has less effect once lactation has begun because the number of progesterone receptors has decreased significantly (also related to the precipitous drop in estrogen). Once lactation has begun, progesterone, which has a greater affinity for milk fat than for the progesterone receptor, is cleared rapidly.
Inhibition of lactation postpartum can be accomplished medically by utilizing bromocriptine(an ergot alkaloid which is a dopamine agonist) at 2.5 mg bid for two weeks, although this not necessary and may be dangerous in women with hypertension. Breast-binding, ice, and avoidance of nipple stimulation will result in cessation of lactation in one week.
Prolactin Actions
Evaluation of Prolactin
When evaluating prolactin levels, physiologic alterations or conditions may result in transient as well as persistent elevations in prolactin levels. Disorders categorized as physiologic conditions and drug-related do not always require intervention.
Plasma levels of immunoreactive prolactin are 5-27 ng/ml during the menstrual cycle. Samples should not be drawn soon after the patient awakes or after procedures. Prolactin is secreted in a pulsatile fashion with a pulse frequency ranging from about 14 pulses per 24 hours in the late follicular phase to about nine pulses per 24 hours in the late luteal phase. There is also a diurnal variation with the lowest levels occurring the midmorning after the patient awakes. Levels rise 1 hour after the onset of sleep and continue to rise until peak values are reached between 5:00 and 7:00 AM (29,30). The pulse amplitude of prolactin appears to increase from early to late follicular and luteal phases (31-33). Because of the variability of secretion and inherent limitations of radioimmunoassay, an elevated level should always be rechecked. This is preferably drawn midmorning and not after stress, venipuncture,breast stimulation, or physical examination, which increases prolactin levels.
Prolactin and TSH determinations are basic evaluations in infertile women. Infertile men with hypogonadism also should be tested. Likewise, prolactin levels should be measured in the evaluation of amenorrhea, galactorrhea, galactorrhea with amenorrhea, hirsutism with amenorrhea, anovulatory bleeding, and delayed and precocious puberty.
Lactation
Prolactin, the major hormone in lactogenesis, is modulated by a combination of second messenger activities which include cyclic nucleotides, prostaglandin, and calcium ion charges,polyamine production, and growth factors. In pregnancy cAMP and cGMP increase progressively and may be involved in stimulation of mitogenic and morphogenic processes that occur with pregnancy. At delivery cAMP levels fall precipitously, and cGMP levels continue to rise and stay elevated in the lactational period. cAMP stimulators abolish prolactin effects,while cGMP increases (marginally) the activity of prolactin. Prolactin certainly does not work via cAMP nor cGMP, but its activity may be modulated by cGMP.
Prolactin can cause perturbations in phospholipid metabolism via the activation of phospholipase enzymes in the cell membrane. Consequent to this action, protein kinase C maybe activated and modulate prostaglandin production and/or intracellular calcium ions.
As mentioned previously, prolactin increases enzyme activities and results in increased polyamine synthesis with resultant increased message and synthesis of products required for lactation.
Growth factors, such as insulin-like growth factor and epidermal growth factor, have been reported to cause mitogenesis in mammary cells and may play a role in the effects of prolactins.
September 1 2006 at 2:21 PM chocogirl (Login chocogirl)
SENIOR MEMBER
--------------------------------------------------------------------------------
Breast changes during physiological hormonal fluctuations influencing the actions of prolactin
Puberty
The major influence on breast growth during puberty is estrogen, which acts by the development of prolactin-dependent estrogen receptors. In most women the first response to rising estrogen levels is an increase in size, pigmentation of the areola, and the formation of abreast mass beneath the areola (thelarche). The primary effect of estrogen is to stimulate growth in the ductal portion of the gland. This growth can begin at any age between 8 to 14 years and normally occurs in a span of four years. Normal development requires prolactin,estrogen, progesterone, growth hormone, insulin, cortisol, thyroid and parathyroid hormone,and growth factors; but this growth is only in anticipation of the development of the fully functional status characterized by full development of the alveoli which occurs only during pregnancy.
Premature thelarche is characterized by the nonprogressive nature and absence of other secondary sexual characteristics. Confirmation is obtained by a normal FSH, LH, prepubertal estrogen concentration, immature vaginal maturation index, and a negative ultrasound exam to rule out ovarian pathology. If other secondary sexual characteristics are noted, a hand film for bone age and a GnRH stimulation test are performed to document precocious puberty.
Cyclic changes in estrogen/progesterone during the normal menstrual cycle result in continued development of breast structures. As estrogen and progesterone levels fall near the end of the cycle, prolactin-induced secretory changes become evident in the alveolar lumen during the first few days of the menses. The breasts are largest in this phase and are smallest on days 4to 7 of the cycle, which is the ideal time for breast self-exam.
Pregnancy
Differentiation of the breast to its mature functional status occurs by the third month of pregnancy. The true glandular acini (true alveoli) develop under the influence of prolactin,human placental lactogen, estradiol, progesterone, insulin, cortisol, growth hormone, IGF-1,and EGF. Thyroid hormones also promote alveolar growth of the glands.
Pregnancy provides a unique opportunity to evaluate the facilitator and inhibitory actions of various hormones; specifically, the interactions of prolactin, estradiol, and progesterone on the development of the lactating breast.
In humans, prolactin acts to (1) increase arginase activity, (2) stimulate ornithine decarboxylase activity, and (3) enhance the rate of transport of polyamines into the mammary gland. All result in increased spermine and spermidine synthesis (polyamines) which are required for milk production. The polyamines stabilize membrane structures, increase transcriptional and translational activities, and regulate enzymes. Prolactin in cultured mammary gland explants also elicits increased messages and synthesis of casein, spermidine,lactose, and phospholipids which are all required for lactation. Estradiol levels, rising throughout pregnancy, act at the hypothalamic level to increase prolactin secretion.
Progesterone interferes with prolactin action at the alveolar cell's prolactin receptor level. While estrogen and progesterone are required to get full activity of the prolactin receptor,progesterone antagonizes the positive action of prolactin on its receptor by (1) inhibiting up regulation of the prolactin receptor, (2) reducing estrogen binding (lactogenic activity), and (3)competing for binding at the glucocorticoid receptor.
Actual lactation occurs after birth by allowing prolonged prolactin elevation without progesterone inhibition because of the more rapid clearance of progesterone in contrast to prolactin. It takes approximately seven days for prolactin to reach non-pregnant levels, while estrogen and progesterone elevations are cleared in three to four days postpartum.
In the first week postpartum, prolactin levels decline 50% (to about 100 ng/ml). Suckling results in increased prolactin, which is important in the initiation of lactation. Until approximately two to three months postpartum, basal levels are 40 to 50 ng/ml in the lactating female, and there are large (10 to 20-fold) increases with suckling. Basal prolactin levels remain normal or slightly elevated with a twofold increase with suckling in the third to sixth months postpartum. Increased prolactin levels are required for lactogenesis; however,nonpregnant levels are adequate to maintain lactation.
Progesterone, while still present postpartum, has less effect once lactation has begun because the number of progesterone receptors has decreased significantly (also related to the precipitous drop in estrogen). Once lactation has begun, progesterone, which has a greater affinity for milk fat than for the progesterone receptor, is cleared rapidly.
Inhibition of lactation postpartum can be accomplished medically by utilizing bromocriptine(an ergot alkaloid which is a dopamine agonist) at 2.5 mg bid for two weeks, although this not necessary and may be dangerous in women with hypertension. Breast-binding, ice, and avoidance of nipple stimulation will result in cessation of lactation in one week.
Prolactin Actions
Evaluation of Prolactin
When evaluating prolactin levels, physiologic alterations or conditions may result in transient as well as persistent elevations in prolactin levels. Disorders categorized as physiologic conditions and drug-related do not always require intervention.
Plasma levels of immunoreactive prolactin are 5-27 ng/ml during the menstrual cycle. Samples should not be drawn soon after the patient awakes or after procedures. Prolactin is secreted in a pulsatile fashion with a pulse frequency ranging from about 14 pulses per 24 hours in the late follicular phase to about nine pulses per 24 hours in the late luteal phase. There is also a diurnal variation with the lowest levels occurring the midmorning after the patient awakes. Levels rise 1 hour after the onset of sleep and continue to rise until peak values are reached between 5:00 and 7:00 AM (29,30). The pulse amplitude of prolactin appears to increase from early to late follicular and luteal phases (31-33). Because of the variability of secretion and inherent limitations of radioimmunoassay, an elevated level should always be rechecked. This is preferably drawn midmorning and not after stress, venipuncture,breast stimulation, or physical examination, which increases prolactin levels.
Prolactin and TSH determinations are basic evaluations in infertile women. Infertile men with hypogonadism also should be tested. Likewise, prolactin levels should be measured in the evaluation of amenorrhea, galactorrhea, galactorrhea with amenorrhea, hirsutism with amenorrhea, anovulatory bleeding, and delayed and precocious puberty.
Lactation
Prolactin, the major hormone in lactogenesis, is modulated by a combination of second messenger activities which include cyclic nucleotides, prostaglandin, and calcium ion charges,polyamine production, and growth factors. In pregnancy cAMP and cGMP increase progressively and may be involved in stimulation of mitogenic and morphogenic processes that occur with pregnancy. At delivery cAMP levels fall precipitously, and cGMP levels continue to rise and stay elevated in the lactational period. cAMP stimulators abolish prolactin effects,while cGMP increases (marginally) the activity of prolactin. Prolactin certainly does not work via cAMP nor cGMP, but its activity may be modulated by cGMP.
Prolactin can cause perturbations in phospholipid metabolism via the activation of phospholipase enzymes in the cell membrane. Consequent to this action, protein kinase C maybe activated and modulate prostaglandin production and/or intracellular calcium ions.
As mentioned previously, prolactin increases enzyme activities and results in increased polyamine synthesis with resultant increased message and synthesis of products required for lactation.
Growth factors, such as insulin-like growth factor and epidermal growth factor, have been reported to cause mitogenesis in mammary cells and may play a role in the effects of prolactins.