Plasma prolactin doesn't correlate with volumes of milk secretion during lactation

Prolactin overview

Prolactin, a protein hormone, is primarily synthesized and secreted by lactotroph cells in the anterior pituitary gland, but also by various extrapituitary tissues like the brain, immune system, uterus, and prostate. Its main role is the regulation of lactation, but a growing number of biological processes are attributed to prolactin.

These include reproduction, metabolic homeostasis, immune function, neuroprotection, body weight control, adipose tissue, skin and hair follicles, pancreas, bone, the adrenal response to stress, and even paternal behavior.

Prolactin signaling occurs via the prolactin receptor, which is expressed in many tissues and is similar to other cytokine receptors.

How to measure your patient's serum prolactin

Prolactin levels in normal non-breastfeeding individuals tend to rise in response to physiological stimuli, including sleep, exercise, and surgical stress. For the most useful results, take the blood sample

• Three or four hours after waking up in the morning, perhaps between 8-10 a.m.

• Rest quietly for half an hour before venepuncture, to make sure that prolactin levels are not elevated due to stress or busy-ness or exercise

• Some medications cause elevated prolactin levels, such as antipsychotics, antidepressants, antihypertensive medications, gastrointestinal medications, and others.

Reproductive phase	Normal prolactin levels (ng/ml)
Non-pregnant female	< 25 ng/ml, or sometimes represented 2-30 ng/ml
Third trimester	20-210 ng/ml
Pregnant at term	200 ng/ml
Lactation	Around 100 ng/ml, decreasing
Six months postpartum and lactating	50 ng/ml

Prolactin levels during lactation

• Prolactin secretion is pulsatile and is stimulated by suckling. Prolactin levels decline to basal level when mother is not breastfeeding. Studies find that

  • Plasma prolactin increases to a 30-45 minute peak after commencement of breastfeeding, and then declines to the pre-nursing or basal concentration by about three hours afterwards (if no further suckling has occurred).

  • The rise in plasma prolactin is gradual in response to suckling and not significant until ten minutes after suckling commenced. Another study found that sustained prolactin elevations persists for at least 16 minutes after the peak.

• Prolactin is required for lactation but once lactation is established, there is no correlation between serum prolactin levels (either baseline levels or percentage increase after suckling) and the volume of milk produced in lactating women. Most lactating women have a higher baseline prolactin level than nonlactating women for a number of months and continue to experience suckling-induced peaks when breastfeeding.

• Prolactin levels decline slowly over the course of lactation but remain elevated for as long as the mother breastfeeds, even if she breastfeeds for years. It has been hypothesised that prolactin controls milk production, but in fact prolactin responds in the short-term to nipple stimulation, with levels declining over the duration of lactation, despite no associated decrease in milk production. For the first six months of lactation, rates of milk synthesis bear no relationship to the short-term prolactin response.

How prolactin relates to lactation

Prolactin has been shown to stimulate not only milk synthesis but also cell proliferation.

• Prolactin promotes growth of mammary alveoli, and stimulates lactocytes to synthesise milk components including lactose, casein and lipids.

• Prolactin receptors are downregulated in mammary glandular tissue during periods of elevated progesterone (pregnancy). After delivery, serum progesterone falls, allowing for upregulation of prolactin receptors on lactocytes, enabling lactogenesis.

• Prolactin may be a potential mechanism allowing concurrent regeneration and differentiation of the lactating epithelium and dynamic maintenance and turnover of the secretory tissue during the course of lactation. - Applying the NDC mechanobiological model for the regulation of milk production, I'd propose that elevated prolactin is a necessary hormonal millieu, which switches on the stem cells and regenerative sensitivity of the mammary tissues to mechanical effects of milk removal.

The prolactin receptor

The prolactin receptor (PRLR) is a membrane-bound protein in the cytokine receptor superfamily. It is encoded in humans by the PRLR gene, and is the receptor for prolactin (PRL).

The PRLR can also bind to and be activated by growth hormone and human placental lactogen. The PRLR is expressed in the mammary glands, pituitary gland, and other tissues. It plays an important role in lobuloalveolar development of the mammary glands during pregnancy and in lactation.

Other roles of prolactin in the body

Prolactin is a peptide hormone, primarily produced by pituitary lactotrophs. Estrogen does not impact prolactin's production or secretion. Prolactin, in addition to its role in lactation and other reproductive processes, has been implicated in multiple biological functions. Here are a few examples.

• Prolactin plays important role on immune modulation.

• Prolactin selectively sensitizes nociceptors from female animals and from post-mortem female human donors, suggesting that this sexually dimorphic mechanism may contribute to increased pain experience in women.

• Prolactin can be produced by extra-pituitary tissues such as adipocytes, immune cells and stromal cells of the uterus, where its synthesis and release are regulated by autocrine/paracrine mechanisms independently from regulation of pituitary prolactin.

Selected references

Bernard V, Young J, Binart N. Prolactin - a pleiotropic factor in health and disease. Nat Rev Endocrinol. 2019 Jun;15(6):356-365. doi: 10.1038/s41574-019-0194-6. PMID: 30899100.

Bocianska K, Bochynski H, Markwitz M, Katulski K. Prolactin's diverse physiological roles and the clinical significance of hyperprolactinemia. Ginekol Pol. 2025;96(9):787-792. doi: 10.5603/gpl.105311. Epub 2025 Jun 9. PMID: 40485263.