**3. Limits of reference**

216 Prolactin

waking up (7-9).

prolactin in a normal individual.

biological activity (10-12).

mammary carcinoma, etc.

**2. Effects** 

(7-11).

The nipple suction during breastfeeding favors a bigger amount of hormone synthesis. Besides, it's one of the few physiological systems that have positive feedback, so the

Nipple and areola´s terminal nerves are stimulated when suction occurs. This stimulus travels via afferent nerve pathways to the hypothalamus, proving the prolactin release, by

Prolactin levels during pregnancy rise from its normal value up to 200 or 400 ng/ml. This increase starts around the 8th week in a simultaneous way with the estrogen increasing. The rising in prolactin secretion is due to the suppression that estrogens provoke over dopamine and the direct stimulation of the transcription of the prolactin gene in the hypophysis. (8)

Prolactin shows a circadian and pulsatile rhythm (figure 3) that starts raising 90 minutes after sleep beginning, with maximum peaks at 4-5 hours and it can stay high two hours after

It is known that its discharges are 20-30 minutes intervals and the mean life is 20-30 minutes

The main circulating form is the monomeric prolactin (little prolactin) or native prolactin which is a non-glycosylated monomer that makes up the 80-90% of the total amount of

Another circulating form in the big prolactin (big PRL) which consist in glycosylated dimers or trimers of 40.000-50000 daltons molecular weight, which is supposed to be a deposit form which is rarely detected in serum and which biological activity is nearly non-existent. However, it is detected in hyperprolactinemia without any pathological clinical signs.

Finally, big-big prolactin or macroprolactin wich is a dimer form of the big-PRL joined to IgG immunoglobulin with a molecular weight over 100000 daltons and without any

The prolactin´s main function in women is to stimulate and maintain the puerperal breastfeeding, direct action over acidophilic cells known as lactotrophs cells of the mammary glands (6, 13). Estrogens, GH, corticoids, placental lactogenic hormones and prolactin are needed to increase the ductal system. Estrogens, progesterone and prolactin are needed to develop the lobuloalveolar system, so levels of these hormones should be considered in pathological states as fibrocystic mastopathy, mastodynia (breast pain),

Among its effects over the mammary alveolar cells there is an increase of the lactose

It is related with the reproductive cycle, the pregnancy maintenance and the fetal growth, through an effect over the mother metabolism acting over different effector organs to

synthesis and a higher production of lactose proteins as casein and lactalbumin.

facilitate its functions through synergy or inhibition of other hormones.

presence of prolactin in the organism favors this peptide production.

inhibition of the release of dopamine. (5-9)

In blood, prolactin can be found from the 16th week of fetal life, increasing its levels due to active secretion, as in birth it shows higher amounts to the ones recorded in the mother.

The normal described limits (figure 4 y 5) for healthy population are the following:


Physiological and Pathological Hyperprolactinemia: Can We Minimize Errors in the Clinical Practice? 219

The limits of reference change according to the studied population showing very

In fertile women the levels show a light elevation during ovulation and the luteinic phase, concerning to the follicular phase, corresponding to the endogenous estrogens liberated by the ovaries, which reduce the prolactin inhibitory factor in the hypothalamus increasing the amount of lactotroph cells as demonstrated in rats by stimulation although that effect depends on the dose and duration of the application, but it used to be shown by 24 hours (3,

In postmenopausal woman and elderly men, levels go down, it is not clear if it is due pituitary deficiency or gonadal insufficiency, showing some role in gonadal function and

The presence of different nonspecific stimulus, as the coitus, exercises, stress situations as surgery, insulin hypoglycemia course….can cause variations in prolactin secretion, some of

Because of what we mentioned previously, it is recommended to take from 2 to 3 samples to determine the prolactin level after 9 am to avoid late effects at night and hypoglycemia.

As it has been described before, prolactin is secreted by lactotroph cells from the anterior hypophysis and it is subjected to the dopamine inhibitory effect in the hypothalamus. Any cause which interferes in its synthesis, the transport to the pituitary gland or the action over

the can have an adaptive nature, as them one occurred in hypoglycemia (12).

the dopamine receptors can produce hyperprolactinemia (Table 1).

pronounced individual variations, even in age and sex groups.

12-15).

aging.

**4. Hyperprolactinemia** 

Pregnancy and lactation Breast stimulation

**Hypothalamic diseases** Craniopharyngioma

Eosinophilic granuloma

Nonsecretory pituitary adenoma

**Physiological** 

Meningioma Dysgerminoma Sarcoidosis

Irradiation Vascular causes Pituitary stalk section **Pituitary pathology** Prolactinoma Acromegaly

Stress

This image is propriety of our laboratory and created by us.The data was taken from Fuchs, F. y Koppler A. Endocrinología de la Gestación. 1982. Segunda edición. Salvat Editores,S.A. Capítulo 12. Pag. 249-72

**Figure 4.** Prolactin's limits of reference (I)

This image is propriety of our laboratory and created by us. The data was taken from Tyson JE, Hwang P, Guyda H, Friesen Hg. Studies of prolactin secretion in human pregnancy. Am J Obstet Gynecol 1972;113:14-20.

**Figure 5.** Prolactin's limits of reference (II)

The limits of reference change according to the studied population showing very pronounced individual variations, even in age and sex groups.

In fertile women the levels show a light elevation during ovulation and the luteinic phase, concerning to the follicular phase, corresponding to the endogenous estrogens liberated by the ovaries, which reduce the prolactin inhibitory factor in the hypothalamus increasing the amount of lactotroph cells as demonstrated in rats by stimulation although that effect depends on the dose and duration of the application, but it used to be shown by 24 hours (3, 12-15).

In postmenopausal woman and elderly men, levels go down, it is not clear if it is due pituitary deficiency or gonadal insufficiency, showing some role in gonadal function and aging.

The presence of different nonspecific stimulus, as the coitus, exercises, stress situations as surgery, insulin hypoglycemia course….can cause variations in prolactin secretion, some of the can have an adaptive nature, as them one occurred in hypoglycemia (12).

Because of what we mentioned previously, it is recommended to take from 2 to 3 samples to determine the prolactin level after 9 am to avoid late effects at night and hypoglycemia.
