Prolactin Therapy

Prolactin is a multipurpose hormone with over 300 functions, it has one of the widest ranges of physiological actions of any hormone. In this Page, I will first go into some of prolactin’s physiology (Section A), follow-up with an analysis of its benefits (Section B) and conclude with Prolactin’s negative effects (Section C).

Section A

Physiology: Functions & Anatomy

Prolactin is a peptide hormone made by the pituitary gland and various other parts of the body. It is also referred to as the luteotropic hormone (luteotropin) and PRL. Prolactin is encoded by the PRL gene (Source).  One of its central functions is to assure reproduction by assuring pregnant mothers’ the Prolactin is responsible for the stimulation of milk production in women (lactogenesis) and exceptionally in male mammals.  (Source). (1)

Prolactin is most known for its breast milk connection. When a woman is pregnant, prolactin levels increase by up to 10-20 times the  normal amount.  The levels return to normal within a few weeks after the mother stops breastfeeding. It is the high prolactin during breastfeeding that will make the pregnant mother unable to have ovulation as long as the prolactin in high. When it is tapered off, then she becomes fertile again. Furthermore, prolactin is important for water/salt regulation, metabolism, reproductive behavior, the immune system, hormones, and the brain (Source).

Anatomy

Prolactin is found to be secreted from the uterus, placenta, immune cells, brain, breasts, prostate, skin, and fat tissue (R). Prolactin receptors are present in the breasts, ovaries, pituitary glands, heart, lung, thymus, spleen, liver, pancreas, kidney, adrenal gland, uterus, skeletal muscle, skin and areas of the brain (R).

Types of Prolactin

The body produces 3 different forms of prolactin: little (14kDa), big (16kDa), and big-big (23kDa) prolactin (R). Prolactin is secreted in a pulse-like fashion with a pulse frequency ranging from about 9-14 pulses per 24 hours. The 14 kDa form is most responsive to stimulation or suppression outside the pituitary gland. The 16 kDa form has inhibitory effects on blood vessel and tumor growth (R). The 23 kDa form creates new blood cells (R).

Prolactin Impacts Other Hormones

Elevated levels of prolactin decrease the levels of estrogen in women and testosterone in men. The effects of altered levels of prolactin on sex hormones are much more profound in women, substantially increasing or decreasing estrogen levels (Source). High prolactin concentrations inhibit secretion of GnRH (gonadotropin releasing hormone), thereby decreasing luteinizing hormone and follicle-stimulating hormone (Source)

Normal levels of prolactin in males enhance testosterone secretion and the creation of sperm (Source) Prolactin decreases hepcidin, which can increase blood iron levels (Source) Prolactin indirectly leads to the release Parathyroid hormone-related peptide (PTHrP) (via increasing serotonin synthesis in breasts), causing bone loss (Source).

Normal Levels of Prolactin

The upper threshold of normal prolactin is about 25 µg/L for women and 20 µg/L for men. Prolactin levels below 3 µg/L in women and 5 µg/L in men are considered too low. Prolactin levels may be checked as part of a sex hormone workup since elevated prolactin secretion can suppress the secretion of other hormones like FSH, GnRH, and sex hormones (Source). Ideal levels of prolactin for men are probably between 5-10 µg/L.

Prolactin level blood tests are most accurate if conducted during the midmorning and not after stress, breast stimulation, physical examination, or other prolactin-increasing stimuli. In addition, elevated levels of prolactin should always be rechecked due to the variability of secretion and inaccurate test readings (Source). Prolactin levels rise starting one hour after a person falls asleep until peak amounts are reached between 5:00 and 7:00 AM.  The lowest levels occur during the midmorning after waking. (Source)

 Prolactin Levels in the Blood

Nonpregnant women 4-23 nanograms per milliliter (ng/mL) or 4-23 micrograms per liter (mcg/L) Men3-15 ng/mL or 3-15 mcg/L Pregnant women 34-386 ng/mL or 34-386 mcg/L Children 3.2-20 ng/mL or 3.2-20 mcg/L High Levels of Prolactin Higher levels of prolactin are found in pregnancy and breast feeding (R).

High levels of prolactin in a woman may cause the following conditions: •Abnormal nipple discharge Infertility/Difficulty getting pregnant Low estrogen and progesterone levels (R) Difficulty getting a period Tiredness Headaches NauseaDizziness and Vision problems. A small benign tumor (microprolactinoma) is  also found in the pituitary of over one-third of women with high levels of prolactin.

High prolactin in males can cause the following problem:Infertility Low testosteron, Low sexual desire Erectile dysfunction (Source)

Low prolactin is associated with ovary dysfunction in women. In men low prolactin is associated with: Low testosterone Erectile dysfunction Premature ejaculation Low sperm count Reduced sperm motility Decreased function of seminal vesicles In one study on low prolactin in men, normal sperm function was restored when prolactin levels were raised back to their correct values.

In mice without prolactin receptors, the hair cycle is disrupted such that shedding occurred earlier and there was a reduced duration of the telogen phase (R).

Ways to enhance the endogenous production of Prolactin

Prolactin levels are the highest during sleep, shortly after you wake up, and during times of physical or emotional stress. In a study on female volunteers under hypnosis, prolactin surges resulted from rage or humiliating experiences, but not from the fantasy of nursing.  Interestingly, compared to single males, fathers generally have higher prolactin concentrations (Source).

The most consistent stimulus for prolactin secretion in males is stress (R). Production of the prolactin-receptor in the brain increases with age, exposure to estrogens, elevation in prolactin levels, and by contact with babies (R).

Below a list where conditions increased prolactin: •Pregnancy•Stress •Depression •Ovulation •Trauma Surgery Tumors of the pituitary gland (prolactinomas) Hypothyroidism Kidney disease Liver disease Seizures Antipsychotics (via blocking DRD2 receptors) (R).Some drugs and medications

Activities that increase prolactin:  Nipple stimulation, Orgasms Exercise (R) and Lactate (R) Sauna (R) Eating

Hormones that increase prolactin: Estrogen Testosterone TRH (R) Progesterone – increases prolactin synthesis in the endometrium and decreases it in the myometrium and breast glandular tissue Vitamin D/Calcitriol (R) Low DHEA Activating the serotonin receptors 5HT2A and 5HT2C

What Decreases Prolactin

Low prolactin can be caused by (R): Damage to the pituitary gland Sleep deprivation Hypopituitarism High Dopamine/D2 receptor activator Hormones that decrease prolactin: Dopamine DHEA Melatonin (R) Supplements that decrease prolactin: Mucuna (dopaminergic) Ginseng Uridine + Glutamine (R) Ginko Balboa (R) Dopamine

The primary Prolactin Inhibiting Factor (PIF) is the neurotransmitter dopamine.  When prolactin is produced, the secretion of dopamine increases as well, which then restricts prolactin production. Thus, treatment with dopamine or compounds that activate dopamine receptors suppresses prolactin secretion.

Estrogen & Progesterone Boosts Prolactin in Women

Studies have shown that increased levels of estrogen correlate to higher amounts of prolactin secretion.  This is confirmed by the fact that women have higher levels of prolactin in their blood during stages of pregnancy and their reproductive cycle when estrogen levels are higher too. Estrogen enhances the growth of prolactin-producing cells, stimulates prolactin production directly, and suppresses the production of dopamine. Progesterone increases and decreases prolactin, depending on the area of the body.

Section B

Benefits

1) Prolactin Helps Create Breast Milk

Milk production occurs after birth by allowing prolactin levels to remain elevated while progesterone and estrogen undergo an abrupt drop as they are rapidly cleared in 3-4 days after birth from the body. Estradiol acts at the hypothalamic level to increase prolactin secretion (R).

In the process of milk production, prolactin, along with cortisol and insulin, act together to stimulate genes that encode milk proteins. Together, they stimulate the uptake of various amino acids and glucose, and the synthesis of the milk proteins (casein), fats, sugar (lactose), spermidine, and phospholipids, which are required for milk production. Non-pregnant levels of prolactin are sufficient to maintain milk production (RR).

In breastfeeding mothers, prolactin is mainly secreted in response to stimulation of the nipples and breast by a suckling infant.  The suckling by the baby blocks the secretion of hypothalamic dopamine (which normally inhibits prolactin). This results in a sharp rise in prolactin concentrations in the blood, followed by a prompt fall when feeding stops (R).

The suckling activates mechanoreceptors in and around the nipple and these signals are carried by nerve fibers through the spinal cord to the hypothalamus (R). High prolactin can cause bone loss in order to export calcium to the breast milk (R, R, R, R, R).

Biochemically, prolactin activates the Jak2/STAT5 pathway, which is responsible for milk production. (2) Prolactin Plays a Role in Breast Development

Prolactin is merely a player in an orchestra of hormones and growth factors that supports breast development (R). Normal breast development requires prolactin, estrogen, progesterone, growth hormone, insulin, cortisol, thyroid and parathyroid hormone, IGF-1, and EGF.  All of these together result in a functional gland. Increased concentrations of prolactin in the blood during pregnancy cause enlargement of the mammary glands in order to prepare for milk production (R).

3) Prolactin Makes You More Nurturing and Influences Sexual Desire

In humans, high prolactin levels are associated with nurturing and parenting behaviors, as well psychosomatic reactions including false pregnancy (R).Prolactin may have a role in paternal care as well (in fish and birds).  In species where the male plays some role in the rearing of the offspring (rats), including humans, studies have found an association between prolactin and paternal care (RR).

In women, prolactin can both increase or decrease sexual desire, and this depends on various factors.  In men, prolactin suppresses sexual behavior in rats (R).

4) Prolactin Helps Fetal Brain Development

Prolactin stimulates the growth, development, and metabolism of the fetus.  It also stimulates the formation of myelin coatings on axons in the brain (R).

Prolactin promotes neurogenesis in the mother and her fetus, immune tolerance of the fetus during pregnancy and contributes to the development of the fetal lungs (R).

5) Prolactin Helps Fertility (sometimes)

Since prolactin increases progesterone, it helps to sustain pregnancies (RR).

However, unusually high levels during pregnancy are associated with spontaneous abortion (R, R).

Thus, high prolactin concentrations during breast feeding reduce fertility, protecting women from a premature pregnancy (R).

At lower levels, prolactin can contribute to male fertility in mice (R), but high prolactin causes infertility in males.  It can also cause low testosterone, a lack of sexual desire, or erectile dysfunction (R).

1) Prolactin and Electrolyte Balance

Prolactin is responsible for fluid, sodium, chloride, and calcium transport across intestinal epithelial membranes (R).

Prolactin acts on the kidney to promote sodium, potassium, and water retention (R).

2) Prolactin Is an Important Hormone During Sex

Prolactin provides the body with sexual gratification after sexual acts.  The hormone counteracts the effect of dopamine, which is responsible for sexual arousal. This is thought to cause the sexual refractory period (R).

The amount of prolactin can be an indicator of the amount of sexual satisfaction and relaxation. Unusually high amounts are suspected to be responsible for impotence and loss of libido (R).

Prolactin levels have also been found to rise with use of the drug MDMA (Ecstasy) (R).

3) Prolactin Increases Neurogenesis

In rats, prolactin can induce neurogenesis in the subventricular zone and the dentate gyrus (R).

Section C

Prolactin in Excess can be Deleterious

Many of the metabolic and immune functions of prolactin can be observed in males, but for some of effects prolactin might not be high enough to be significant (R).

1) Prolactin is an Immune Stimulant

Prolactin affects a large number of cytokine receptors (R) and acts in a cytokine-like manner, increasing the production of many immune system cells (R).

Prolactin is mostly an immune stimulant. The hormone plays a role in autoimmune diseases.

Some types of lymphocytes secrete prolactin and this allows for production of more lymphocytes (R,R,R).  Lymphocytic prolactin plays a role in skin graft rejection (R).

Immune responses (B cell, T cell) in organisms are enhanced by prolactin (R).

Prolactin increases cytokine secretion and inhibits the suppressor effect of regulatory T (Treg) cells in healthy individuals (R).

Treg cells help create tolerance and an anti-inflammatory environment.

Prolactin stimulates T effector cells (not good for autoimmune) and increases IFNy secretion, which encourages an inflammatory environment and Treg cell malfunction (R).

However, prolactin deficiency can cause immunodeficiency (R).

Interestingly, mice without the prolactin gene fail to show significant abnormalities in immune responses.  As a result, prolactin has a modulatory role in several aspects of immune function but is not strictly required for these responses (R).

2) Prolactin Can be an element in the causation of Autoimmune Disease

Excess prolactin is one of the important factors in the development and course of autoimmune diseases such as (R, Source): Autoimmune thyroid disease Alopecia (R) Systemic lupus erythematosus (R) Rheumatoid arthriti Psoriasis (R) Systemic sclerosis Polymyalgia rheumatica Sjogren’s syndrome – excess prolactin is diagnosed in nearly one-third of these patients Psoriatic arthritis – Drugs that lower prolactin help and improve joint and skin symptoms (R).

3) Prolactin Can Cause Weight Gain and Hunger

Prolactin receptors are found in fat tissue, liver, pancreas and the brain (R).

In fat tissue, prolactin is essential in fat cell production. It also increases the secretion of leptin and inhibits adiponectin (R).

Prolactin promotes appetite and contributes to the rapid increase in food intake during pregnancy and nursing (R).

In the pancreas, it increases insulin secretion (from glucose) and glucose sensitivity (R). This helps prevent diabetes during pregnancy, but can cause weight gain (R).

Prolactin also induces functional leptin resistance, which would contribute to increased food intake, potentially mediating the well-established leptin resistance of pregnancy (R).

Patients with high prolactin are prone to excessive weight gain, and normalization of prolactin levels using dopamine activators is associated with weight loss (R).

Interestingly, gene studies have revealed that a common variant adjacent to the prolactin gene is associated with obesity (R).

4-5) Prolactin Can Cause Anxiety and Depression

A byproduct of prolactin (vasoinhibins) causes depression and anxiety.

There is a correlation between prolactin and anxiety in men (R).

Prolactin levels in unipolar depressive patients are related to dissociative symptoms (R).

Prolactin may cause mood issues because of it regulates receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency (R).

6) Prolactin May Worsen Migraines and Cause Pain

High prolactin may contribute to the pain in migraines, which can subside when given a drug to decrease prolactin (R).

Women given a drug to lower prolactin experienced improvement in their migraines (R).

7) Prolactin Inhibits Blood Vessel Growth

Prolactin increases vasoinhibins, which are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation (R).

Disturbances of the prolactin/vasoinhibin axis are associated with the development of retinal diseases, cardiac diseases, and diseases occurring during pregnancy (R).

8) Prolactin May Cause Cystic Fibrosis

Prolactin is one of the possible causes in cystic fibrosis (R).

9) Prolactin May Increase Cancer Risk. Prolactin may increase breast and prostate tumors (R).

Discussion

In zoology, male lactation is the production of milk from a male mammal’s mammary glands in the presence of physiological stimuli connected with nursing infants. Such production is known as lactation. It is well-documented in the Dayak fruit bat. The term male lactation is not used in human medicine. It has been used in popular literature, such as Louise Erdrich’s The Antelope Wife, to describe the phenomenon of male galactorrhea, which is a well-documented condition in humans, unrelated to childbirth or nursing. Newborn babies of both sexes can occasionally produce milk; this is called neonatal milk (also known as “Witch’s milk”) and not considered male lactation.

Male lactation was of some interest to Alexander von Humboldt, who reports in Voyage aux régions équinoxiales du Nouveau Continent of a citizen of the village Arenas (close to Cumana) who allegedly nurtured his son for three months when his wife was ill, as well as Charles Darwin, who commented on it in The Descent of Man, and Selection in Relation to Sex (1871):

It is well known that in the males of all mammals, including man, rudimentary mammae exist. These in several instances have become well developed, and have yielded a copious supply of milk. Their essential identity in the two sexes is likewise shown by their occasional sympathetic enlargement in both during an attack of the measles. (Source). 

Darwin later considered the nearly perfect function of male nipples in contrast to greatly reduced structures such as the vesicula prostatica, speculating that both sexes may have nursed young in early mammalian ancestors, and subsequently mammals evolved to inactivate them in males at an early age. (Source).

Male mammals of many species have been observed to lactate under unusual or pathogenic conditions such as extreme stress, castration and exposure to phytoestrogens, or pituitary tumors. Therefore, it is hypothesized that, while most male mammals could easily develop the ability to lactate, there is no selective advantage to male lactation. While male mammals could, in theory, improve offspring’s survival rate through the additional nourishment provided by lactation, most have developed other strategies to increase the number of surviving offspring, such as mating with additional partners. Presently, very few species are known where male lactation occurs and it is not well understood what evolutionary factors control the development of this trait. (Source).

The phenomenon of male lactation occurs in some species, notably the Dayak fruit bat (Dyacopterus spadiceus), and the lactating males may assist in the nursing of their infants. In addition, male goats are known to lactate on occasion. (Source).

Human male breastfeeding is possible, but production of the hormone prolactin is necessary to induce lactation, so male lactation does not occur under normal conditions. (Source). Domperidone is a drug that can be used to increase lactation. Male lactation has also been seen during recovery from starvation. This may be because glands that produce hormones recover faster than the liver, which absorbs hormones, leading to high hormone levels.(Source)

Spontaneous production of milk not associated with childbirth, known as galactorrhea, can occur in males and females. (Source). We call galactagogue substances that can stimulate mammary glands to produce human milk.

All of these facts are relevant to health and longevity because human milk is suppose to be the evolutionary based “perfect” food.

Conclusion

Under construction

Reference and Precision Notes

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