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Prolactine Deficiency
Vilnius, 11. August 2010
The vast majority of hypoprolactinemic states occur secondary to general anterior pituitary dysfunction. The most commonly associated condition is postpartum pituitary necrosis (Sheehan syndrome); however, prolactin deficiency can also be caused by anterior pituitary impairment secondary to pituitary (or extrapituitary) tumor or treatment of tumor, parasellar diseases, head injury, infection (eg, tuberculosis, histoplasmosis), or infiltrative diseases (eg, sarcoidosis, hemochromatosis, lymphocytic hypophysitis).
Partial isolated prolactin deficiency is rare, and case reports of total isolated prolactin deficiency are rarer still and may have a genetic component (ie, familial puerperal alactogenesis). Although the endocrine and metabolic function of prolactin is not fully understood, the clinical manifestation of prolactin deficiency is probably limited to puerperal alactogenesis.
Prolactin deficiency is characterized by the inability of pituitary lactotrophs to secrete prolactin and the resulting lack of puerperal lactogenesis. Other pathophysiologic mechanisms have not been fully established. Prolactin is principally regulated by tonic inhibition rather than by intermittent stimulation. Its principal inhibitory regulator is dopamine. Prolactin enhances dopamine secretion and, thus, exhibits feedback inhibition of its own secretion. The only other known physiologic inhibitors include triiodothyronine (T3) and somatostatin.
Menstrual disorders, delayed puberty, infertility, and subfertility have also been associated with hypoprolactinemia through mechanisms that are not entirely clear. Prolactin concentration in follicular fluid during in vitro fertilization (IVF) correlates with the oocyte maturation level and fertilization rate. Further, in a randomized human trial, bromocriptine-induced hypoprolactinemia during IVF resulted in decreased fertilization and cleavage rate compared with a hyperprolactinemic cycle group. A partial prolactin deficiency may result in inadequate lactation. Further, a possibility exists that male factor infertility may be associated with hypoprolactinemia. Serum prolactin levels that were suppressed by bromocriptine resulted in decreased spermatogenesis and decreased testosterone production in healthy male volunteers.
Some data support the idea that prolactin is also an immunoregulating hormone. Prolactin receptors have been found on human T lymphocytes and B lymphocytes, and some data support T lymphocyte dependence on prolactin for maintenance of immune competence. Using a mouse model, inhibition of prolactin release impaired lymphocyte function and depressed macrophage activation. Further, these mice had a decreased tolerance for bacterial exposure that was manifest by death from a normally nonlethal dose. Part of the immunosuppressive effects of cyclosporin may be mediated through a competitive antagonistic action at the prolactin receptor site. Further evidence is found in the observation of the immunosuppressant effects of bromocriptine, which has been shown to be an effective adjuvant (immunosuppressant) in patients after transplantation and in patients with autoimmune disease.
Because prolactin release is inversely related to dopamine levels in the anterior pituitary, critically ill patients on prolonged dopamine infusion have resultant prolactin deficiency. This has been hypothesized to be the cause of the T lymphocyte proliferation response impairment that occurs in patients in an ICU and may be an important cause of infection susceptibility in this group; however, no data support the hypothesis that lack of prolactin in otherwise healthy patients results in immunodeficiency.
Finally, in preterm infants, several studies have correlated hypoprolactinemia with increased mortality. The precise pathophysiologic mechanism is unknown, but it is speculated to be associated with the effects of prolactin on surfactant synthesis, whole body water regulation, or gastrointestinal maturation.
Prolactine Deficiency
The vast majority of hypoprolactinemic states occur secondary to general anterior pituitary dysfunction. The most commonly associated condition is postpartum pituitary necrosis (Sheehan syndrome); however, prolactin deficiency can also be caused by anterior pituitary impairment secondary to pituitary (or extrapituitary) tumor or treatment of tumor, parasellar diseases, head injury, infection (eg, tuberculosis, histoplasmosis), or infiltrative diseases (eg, sarcoidosis, hemochromatosis, lymphocytic hypophysitis).
Partial isolated prolactin deficiency is rare, and case reports of total isolated prolactin deficiency are rarer still and may have a genetic component (ie, familial puerperal alactogenesis). Although the endocrine and metabolic function of prolactin is not fully understood, the clinical manifestation of prolactin deficiency is probably limited to puerperal alactogenesis.
Prolactin deficiency is characterized by the inability of pituitary lactotrophs to secrete prolactin and the resulting lack of puerperal lactogenesis. Other pathophysiologic mechanisms have not been fully established. Prolactin is principally regulated by tonic inhibition rather than by intermittent stimulation. Its principal inhibitory regulator is dopamine. Prolactin enhances dopamine secretion and, thus, exhibits feedback inhibition of its own secretion. The only other known physiologic inhibitors include triiodothyronine (T3) and somatostatin.
Menstrual disorders, delayed puberty, infertility, and subfertility have also been associated with hypoprolactinemia through mechanisms that are not entirely clear. Prolactin concentration in follicular fluid during in vitro fertilization (IVF) correlates with the oocyte maturation level and fertilization rate. Further, in a randomized human trial, bromocriptine-induced hypoprolactinemia during IVF resulted in decreased fertilization and cleavage rate compared with a hyperprolactinemic cycle group. A partial prolactin deficiency may result in inadequate lactation. Further, a possibility exists that male factor infertility may be associated with hypoprolactinemia. Serum prolactin levels that were suppressed by bromocriptine resulted in decreased spermatogenesis and decreased testosterone production in healthy male volunteers.
Some data support the idea that prolactin is also an immunoregulating hormone. Prolactin receptors have been found on human T lymphocytes and B lymphocytes, and some data support T lymphocyte dependence on prolactin for maintenance of immune competence. Using a mouse model, inhibition of prolactin release impaired lymphocyte function and depressed macrophage activation. Further, these mice had a decreased tolerance for bacterial exposure that was manifest by death from a normally nonlethal dose. Part of the immunosuppressive effects of cyclosporin may be mediated through a competitive antagonistic action at the prolactin receptor site. Further evidence is found in the observation of the immunosuppressant effects of bromocriptine, which has been shown to be an effective adjuvant (immunosuppressant) in patients after transplantation and in patients with autoimmune disease.
Because prolactin release is inversely related to dopamine levels in the anterior pituitary, critically ill patients on prolonged dopamine infusion have resultant prolactin deficiency. This has been hypothesized to be the cause of the T lymphocyte proliferation response impairment that occurs in patients in an ICU and may be an important cause of infection susceptibility in this group; however, no data support the hypothesis that lack of prolactin in otherwise healthy patients results in immunodeficiency.
Finally, in preterm infants, several studies have correlated hypoprolactinemia with increased mortality. The precise pathophysiologic mechanism is unknown, but it is speculated to be associated with the effects of prolactin on surfactant synthesis, whole body water regulation, or gastrointestinal maturation.