Pituitary Tumors and Their Management
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
Prolactin-secreting pituitary adenomas are the most common form of pituitary tumor and represent the most common cause of hyperprolactinemia. Prolactin is classified as a somatomammotropic hormone along with GH and chorionic somatomammotropin [13]. It is a peptide chain that is 198 amino acids long, necessary for the normal lactation in postpartum women. Prolactin levels begin to rise shortly after conception and reach levels of 150–200 ng/mL at term; however, it is not until the postpartum decline in estrogen is complete that lactation may occur. Stimulation of tactile receptors on the nipple and areola of the breast leads to prolactin secretion that in the postpartum estrogen-primed breast results in lactation. Hyperprolactinemia disrupts normal reproductive function by altering the pulsatile gonadotropin secretion, interfering with sex steroid feedback at the level of the hypothalamus, and inhibiting gonadal steroidogenesis. TRH and vasoactive intestinal peptide (VIP) both appear to have minor prolactin-releasing activity, although their significance is presently unclear. Although the above stimuli lead to increases in prolactin secretion, the overwhelming control of prolactin release is inhibitory in nature, via dopamine. Dopamine, also known as a PIF, is released by the hypothalamus and leads to a decrease in prolactin secretion. As mentioned earlier, this inhibitory control becomes vitally important in the medical management of prolactinomas [14, 15]. Normal prolactin levels are less than 15 ng/mL in men and less than 20 ng/mL in nonpregnant women. Causes of hyperprolactinemia other than a pituitary adenoma include pregnancy, stress, hypoglycemia, renal failure, hypothyroidism, and phenothiazine-like medications. These, as well as several other etiologies, must be considered prior to a detailed investigation of a patient’s pituitary gland [16].
Maternal obesity
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Interesting work reveals an association between obesity and breast-feeding failures even after controlling for socioeconomic status (42,43). Increased prepregnancy BMI is associated with shorter breast-feeding duration (42). This is unfortunate as both maternal obesity and short duration of breast-feeding are independent risk factors for childhood overweight (43). Recently, biologic data support this epidemiologic association between obesity and short duration of breast-feeding. Increased prepregnancy BMI predicts a lower prolactin response to suckling at 48 hours. Prolactin is responsible for stimulating milk production and thus a decrease in responsiveness could lead to a diminished ability to make milk and perhaps contribute to breast-feeding discontinuation (44). Perhaps interventions that improve prepregnancy BMI and or maternal weight gain might improve a woman’s ability to breast-feed.
Hypothalamic Neuroendocrine Regulation
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
Prolactin is an anterior pituitary hormone that acts directly on target tissue rather than as a tropic hormone. Although prolactin plays many physiologic roles in other animals, its known function in humans is postpartum stimulation of milk production. It is, however, present in males and nonpregnant females, where its function is unknown. In addition, bursts of prolactin release occur in sleep and during stress. Unlike other pituitary hormones, prolactin is regulated mainly by tonic inhibition rather than by intermittent stimulation. The neurotransmitter dopamine appears to fit the criteria of a prolactin releasing inhibitory factor. Hence, prolactin’s principal inhibitor is dopamine. Prolactin enhances dopamine secretion and thus inhibits its own secretion. Other known physiologic inhibitors are somatostatin and triiodothyronine. Prolactin release is stimulated by serotonin, acetylcholine, opiates, estrogens, TRH, and angiotensin-II. Which of these is physiologically important is not known.
Therapeutic potential of S179D prolactin – from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator
Published in Expert Opinion on Investigational Drugs, 2006
Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review focuses on one such antagonist, S179D prolactin, which was produced by mimicking a natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective growth antagonist, partly because it inhibits signalling from unmodified prolactin and partly because it produces its own intracellular signal. This signal results in cell differentiation, cell-cycle arrest or apoptosis depending on dose, duration of treatment and cellular context. S179D prolactin is also a potent antiangiogenic and initial studies have shown it to be a potent anti-inflammatory agent. In light of these additional modes of action, it is suggested that S179D prolactin should now be more aptly referred to as a selective prolactin receptor modulator.
The Brain Prolactin System: Involvement in Stress Response Adaptations in Lactation
Published in Stress, 2002
This review focuses on prolactin as a potential candidate for the regulation of emotional and neuroendocrine stress responses in the brain. In particular, we summarise evidence for a brain prolactin receptor-mediated anxiolytic action both in female and male rats, and for inhibitory actions on the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and the neurohypophysial oxytocin system. These physiological functions of the brain prolactin system are especially relevant in the peripartum period, as an attenuation of behavioural and neuroendocrine stress responses has been described during pregnancy and lactation. At this time, there is an increase in brain prolactin receptor expression and binding, and an increase in hypothalamic prolactin gene expression. In the absence of a selective prolactin receptor antagonist, complementary approaches including chronic intracerebral infusion of prolactin, and antisense targeting of the long form of the brain prolactin receptor were used to investigate the actions of prolactin. The hypothesis of a brain prolactin system activated in the peripartum period which contributes to the adaptive changes in stress responsiveness in order to support reproductive functions is strongly emphasised.
Increased prolactin response to TRH in polycystic ovary syndrome with low basal prolactin values
Published in Gynecological Endocrinology, 1988
A. Szilágyi, T. Csermely, I. F. Csaba
An intravenous TRH loading test with 200 μg TRH was carried out in 9 hypoprolactinemic (serum prolactin < 100 mlU/ml) and 6 normoprolactinemic PCO patients and 6 normal subjects. Basal and stimulated prolactin and TSH levels were measured. The latter were within normal values. Prolactin responses to TRH were exaggerated in PCO patients, irrespective of the basal prolactin values. According to literary data, these results indicate that increased prolactin response to TRH in PCO is independent of the basal prolactin values and suggest disturbed tuberoinfundibular dopaminergic function.