Physiology Of Lactation : Prolactin Hormone

Prolactin Hormone

Prolactin is a 199 amino acid single-chain polypeptide hormone that is transcribed by one gene on chromosome 6. Human placental lactogen (hPL) and growth hormone (GH) share structural similarities with prolactin. Lactotroph cells found in the anterior pituitary secrete prolactin; this pulsatile kind of secretion releases prolactin in intervals of four to fourteen per day. The secretion of prolactin varies throughout the day.

Prolactin Regulation

The hypothalamus releases dopamine, an inhibitory factor, which causes the anterior pituitary to chronically inhibit prolactin secretion. There are specific instances when this inhibition is lifted off, including bodily states like pregnancy. Feedback inhibition is caused by stimuli such as breast or nipple stimulation and nursing. Prolactin secreted by lactotrophs works on multiple target tissues, including the breasts.

Hence, if there is any disruption in the secretion or transmission of dopamine across the pituitary infundibular stalk, it will increase prolactin secretion along with nipple stimulation, and nursing induces the release of prolactin because the neural arch inhibits the dopamine secretion.  The lactotrophs secreting prolactin have a very high activity, and under normal circumstances this prolactin secretion is kept under continuous tonic inhibition from higher centers using factor dopamine.

Endogenous opioids released during stress can also restrict prolactin secretion. Another theory is that some prolactin-releasing factor intermediates in between to boost the release of prolactin. Several mechanisms exist for how estrogen stimulates prolactin release, including the differentiation of lactotrophs, an increase in prolactin gene transcription, and the inhibition of dopamine secretion.

Thyrotropin releasing hormone (TRH) is one of the hypothalamus's additional prolactin-releasing factors. When TRH levels are high, as they are in primary hypothyroidism, prolactin gene transcription is increased and dopamine is inhibited. Dopamine actions: D2 dopamine receptors are present in lactotrophs, which release prolactin.

These D2 receptors are acted upon by dopamine, which causes an inhibitory signal to be sent, which halts the release of prolactin.  medications that are dopamine antagonists, such as cabergoline and bromocriptine, will inhibit prolactin secretion, lowering prolactin levels; Dopamine synthesis inhibitory medications block the impact of dopamine on prolactin, resulting in an increase in prolactin production.

Prolactin In Pregnancy

Neither the growth of the mammary glands during puberty nor the formation of breast tissue depend on prolactin. Later phases of breast growth require it, particularly during pregnancy when it is combined with other hormones like progesterone and estrogen priming.

During pregnancy, there is estrogen-mediated lactotroph hyperplasia, which causes increased prolactin release in the bloodstream and breast milk production. Prolactin hormone is necessary for lactation since it is necessary for milk synthesis.

Decidual prolactin is a separate form of pituitary prolactin release that is not controlled by the circulation of either dopamine or estrogen. Nonetheless, decidual prolactin secretion is stimulated by progesterone secretion.

During pregnancy, progesterone does not control anterior pituitary prolactin release or lactotroph hypertrophy.

More than 20 mg/ml of prolactin is secreted by non-pregnant women. This degree of increase starts to rise about 8 weeks of gestation and continues until the women reach term.

Prolactin reaches its peak at term, when it is 200–400 ng/ml. During gestation, however, there is no active milk secretion, with the exception of colostrum, which contains transubate and desquamate epithelial cells.

 During pregnancy, alveoli—milk-secreting structures—develop in the breast tissues. These alveoli have prolactin receptors on them.  The prolactin receptors belong to the cytokine receptor superfamily and are encoded by a gene found on chromosomal number 5.  When the prolactin hormone attaches to its receptor, the alveoli are affected.One crucial function that estrogen and progesterone perform in the development of the milk-producing apparatus during pregnancy is "the priming of the milk synthesizing apparatus." This indicates that they will control the expression of the prolactin receptor.

Therefore, at the receptor level, progesterone is limiting the binding of receptor and the prolactin hormone, thereby inhibiting the full lactation.  The increased progesterone will prevent prolactin from binding to its receptor. Progesterone at high levels obstructs prolactin and rector binding at the alveolar cells. Progesterone also prevents the formation of α-lactalbumin, which is necessary for the active production of milk. Pharmacologically high amounts of estrogen may also have these effects.

Following delivery, prolactin inhibition is removed due to a decrease in estrogen and progesterone levels, and active milk production can be observed in three to four days.  A drop or reduction in prolactin levels following delivery.

The prolactin level in the blood drops quickly in a non-breastfeeding woman (orange graph), reaching non-pregnant levels in approximately 7 days after giving birth, whereas the reduction is slower in a breastfeeding woman.

Until the woman continues to breastfeed, it is very low for two to three months postpartum, but it is still somewhat over the non-pregnant level. Prolactin secretion is known to spike during periods when the baby is nursing. 

Also Read: Neuroendocrinology Of Female Reproduction And Steroid Hormones

Lactation

There will eventually be a dopamine withdrawal;  Babies nursing on women's breasts transmit signals upstream to higher centers via thoracic nerves, which are the sensory afferents that carry the signals to the higher centers.  Milk is produced into the alveoli and needs to be assisted for the baby. This causes the anterior pituitary to generate more prolactin, which increases milk production. The stimulation that sends sensory afferents to the neural arch, which in turn sends signals to the hypothalamus, will also be the newborn signal.

This time, the signals are directed towards the paraventricular region of the hypothalamus and the supraoptic nucleus, which are in charge of producing oxytocin. After that, they are sent to the posterior pituitary, where they are released. As a result, the myoepithelial cells contract, forcing the milk into the lactiferous ducts and extracting it from the alveoli. This is known as the "milk let-down reflex" or the "milk ejection reflex."

Other signals, such as smells or a baby's scream, can also function as stimuli because the signal is transmitted through the neural arch. resulting in the milk ejection reflex's comparable outcomes.  The mother's milk ejection response occurs into both breasts, regardless of which breast she uses to nurse her infant.

It is during breastfeeding that prolactin and oxytocin are released.  Casein, fatty acids, and lactose production are all maintained by prolactin.  The availability of the thyroid, insulin, IGFs, cortisol, and dietary intake of nutrients and fluids are also necessary for optimal milk quality and quantity.

 Oxytocin empties the alveolar lumen, which enhances subsequent milk secretion and alveolar refilling.  Dopamine antagonists such as metoclopramide and domperidone can be used to induce nursing in order to enhance the expression or synthesis of milk.

Also Read: Pruritus In Pregnancy : Clinical Presentation

Suppression Of Lactation

The suppression of lactation may be crucial in the event of a baby's death or stillbirth. Advise the mother to cease expressing milk and to refrain from stimulating her breasts in any way. Council mother to have her breasts well supported. The alveoli have a 48-hour maximal milk storage period before becoming engorged. Production will be inhibited by the pressure exerted by the enlarged alveoli.

When breastfeeding stops, dopamine production will continue, which will block the flow of prolactin. The mother has pain from her enlarged breasts and engorged alveoli, which may lead to a want to empty her breast—something she shouldn't do.

In addition to tight breast support, cold compressors and analgesics can be recommended for pain management in this situation. The engorgement subsides in a few days as a result of the collected fluid, milk, and solutes being reabsorbed after a few days.

Drugs are the second line of treatment, however they can be administered if necessary. In these circumstances, dopamine agonists are typically used. One milligram of caffeine stops lactation, but two days with 0.25 mg BD suppresses lactation that has already begun. Because bromocriptine increases the risk of stroke, it is not advised. Patients with hypertension cannot take either of these medications.

Effects Of Lactation

 The daily loss of calcium is about doubled by the calcium that is secreted into the milk of nursing women. Bone damage quickly returns to baseline levels in the six months following weaning; routine supplementation is not necessary for women who do not have any deficiencies; increased bone resorption caused by lactation is likely the cause of the bone loss.

Women may complain about vaginal lubrication because of the reduced estrogen levels linked to the postpartum period.

Creams containing estrogen should be avoided since they may affect the production of milk.

Advantages For The Newborn

 In addition to a full and varied diet, human milk helps shield babies from infections by changing the bacterial flora in their gastrointestinal system and by transferring immunoglobulins.

There are T and B lymphocytes in milk. The newborn seems to benefit from the mother's immune expression through memory T cells. Reduced risk of infectious diseases, SIDS, and childhood metabolic diseases like diabetes and obesity.

Contraceptive Effects Of Lactation

This only applies to ladies who meet the criteria for amenorrhoeic women. Women who nurse their infants exclusively for at least one hour each day. Only throughout the first six months of lactation, including at night. The effectiveness of a contraceptive method is 98% if all of these are present.

Return Of Ovulation And Menses 

 Women who are not nursing will often resume their menstrual cycle in six to eight weeks.  Seventy percent of women who breastfeed for six months or longer will still experience amenorrhea.  Even in women who are amenorrheic, supplemental feeding raises the likelihood of ovulation and pregnancy.

The onset of menstruation in nursing mothers can occur as soon as two months after giving birth or as late as eighteen months.  In general, breastfeeding postpones the onset of ovulation. The return of regular menstrual flow is often indicative of the onset of ovulation. Bleeding can be anovulatory; it can happen without ovulation. Approximately 4% of breastfeeding women will become pregnant each year.  For breastfeeding women, total protection from birth control is limited to the first 10 weeks following delivery.

The Rule of Three has to be adhered to. This is the start of postpartum contraception. This states that women who are breastfeeding or who are nursing should begin using contraceptives in the third postpartum month, while women who are not breastfeeding or who are not nursing should begin using within the first three weeks after giving birth.

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