Breast Prolactin

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

This section of the chapter discusses FSH, LH, GH, and ACTH. FSH and LH are called gonadotropins because they influence the gonads (the organs of reproduction). GH, also called somatotropin, contributes to the growth of the body during childhood, especially the growth of muscles and bones. ACTH is produced by the anterior pituitary and stimulates the adrenal cortex to secrete the corticosteroids. The anterior pituitary hormone, TSH, is discussed in Chapter 51. Prolactin, which is also secreted by the anterior pituitary, stimulates the production of breast milk in the postpartum patient Additional functions of prolactin are not well understood. Prolactin is the only anterior pituitary hormone that is not used medically. 

Prolactin is an essential hormone for normal production of breast milk following childbirth. It also plays a pivotal role in a variety of reproductive functions. Prolactin is regulated primarily by the hypothalamus-pituitary axis and secreted solely by the lactotroph cells of the anterior pituitary gland. Under normal conditions, secretion of prolactin is predominantly under inhibitory control by dopamine and acts on the D2 receptors located on the lactotroph cells. Increase of hypothalamic thyrotropin-releasing hormone (TRH) in primary hypothyroidism can stimulate the release of prolactin. 

After birth, a rapid drop in progesterone level initially triggers lactation through reversal of inhibitory effects on prolactin (Fig. 44-2). Nipple stimulation then enables lactation to continue once established. During lactation, ineffective removal of milk from the breast, trauma, and skin breaks may lead to problems such as milk stasis, nipple pain, and mastitis.12 Additionally, some women have difficultly initiating lactation due to improper technique and/or activity of inhibitors such as dopamine (Fig. 44-2). 

Yet different elaboration of the same molecule affords a compound (162) that acts as an inhibitor to the pituitary peptide hormone prolactin, the factor responsible for supporting lactation. As such the drug has found use in suppressing lactation and in the treatment of prolactin-dependent breast tumors. 

The release of prolactin from the adenohypophysis is normally inhibited by prolactin-inhibiting hormone (PIH, dopamine) from the hypothalamus. Prolactin secretion is also controlled by prolactin-releasing factor (PRF). The release of PRF from the hypothalamus is mediated by reflexes elicited by suckling and breast stimulation. 

Nissen, E., Uvnas-Moberg, K., Svensson, K., Stock, S, Widstrom, A. M., and Winberg, J. 1996. Different patterns of oxytocin, prolactin but not cortisol release during breast feeding in women delivered by caesarean section or by the vaginal route. Early Human Development, in press. 

Lactoferrin is the major whey protein present in breast milk (Teraguchi et ah, 1996) with many microbicidal properties (Leon-Sicairos et ah, 2006). The concentration of lactoferrin in milk has been reported as 1 g/liter in mature milk and 7 g/liter in colostrum (Houghton et ah, 1985). The concentration of lactoferrin in breast milk is controlled by the reproductive hormones prolactin and estrogen (Ward et ah, 2005). Lactoferrin has been demonstrated to resist digestion in the infant gut as it has been recovered intact from the stool of breast-fed infants (Bemt and Walker, 1999). Lactoferrin acts mainly in an iron-free state (apo-lactoferrin) and its microbicidal activity is reported to increase in proportion to its concentration in milk (Leon-Sicairos et ah, 2006). 

Endocrine Prolactin elevation Dopamine 2 Obtain prolactin level for patients with breast enlargement, menstrual abnormalities, or gynecomastia... 

The dopamine neurons that project from the hypothalamus to the anterior pituitary are known as the tuberoinfundibular dopamine pathway (Fig. 10—13). Normally, these neurons are active and inhibit prolactin release. In the postpartum state, however, their activity is decreased, and therefore prolactin levels can rise during breastfeeding, so that lactation will occur. If the functioning of tuberoinfundibular dopamine neurons is disrupted by lesions or drugs, prolactin levels can also rise. Elevated prolactin levels are associated with galactorrhea (breast secretions), amenorrhea,... 

A 29-year-old woman with a schizoaffective disorder took haloperidol 5 mg/day and then 9 mg/day because of acute psychotic episodes. She had no adverse effects such as amenorrhea or galactorrhea. Haloperidol was then replaced by aripiprazole 15 mg/day and on the evening of the second day she developed breast tenderness and marked galactorrhea. The serum prolactin concentration was 32 ng/ml (reference range 5-25 ng/ ml). Aripiprazole was withdrawn and haloperidol restarted. The galactorrhea resolved in 1 week. 

There is concern that neuroleptic drugs may increase the risk of breast cancer because of raised prolactin concentrations. For a long time, findings did not confirm this association (752), but a Danish cohort study of 6152 patients showed a slight increase in the risk of breast cancer among schizophrenic women (753). 

In women reserpine causes a small increase in circulating concentrations of prolactin (1006), which could be related to the small increase in the risk of breast cancer. In 27 hypertensive men reserpine 0.25 mg/day for 3 months had no effect on testosterone, dihydrotestosterone, estradiol, luteinizing hormone, or prolactin (1007). 

Schyve PM, Smithline F, Meltzer HY. Neuroleptic-induced prolactin level elevation and breast cancer an emerging clinical issue. Arch Gen Psychiatry 1978 35(11) 1291-301. 

Ross RK, Paganini-Hill A, Krailo MD, Gerkins VR, Henderson BE, Pike MC. Effects of reserpine on prolactin levels and incidence of breast cancer in postmenopausal women. Cancer Res 1984 44(7) 3106-8. 

Are breast-feeding. Melatonin affects the level of prolactin, a hormone that controls the production of breast milk. 

Dietary Fat, Prolactin, and Breast Cancer. Prolactin may also interact with diet to influence breast cancer. Although the role of prolactin in human breast cancer etiology is relatively obscure, its role as a promotor in rodent mammary carcinogenesis has been well established (55,56). 

---