Rethinking the stalk effect: A new hypothesis explaining suprasellar tumor-induced hyperprolactinemia

Skinner, Donal C.

doi:10.1016/j.mehy.2008.08.030

Cited by 22 publications

(11 citation statements)

References 10 publications

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“…Earlier studies have reported Substance P and NKA in the ovine PT and had suggested that these peptides could act as PRL secretagogues [20, 21]. Previous studies in rodents showed that Substance P and NKA can act as potent regulators of pituitary hormone secretion.…”

Section: Resultsmentioning

confidence: 99%

Identification of Eya3 and TAC1 as Long-Day Signals in the Sheep Pituitary

et al. 2010

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Summary Seasonally breeding mammals such as sheep use photoperiod, encoded by the nocturnal secretion of the pineal hormone melatonin, as a critical cue to drive hormone rhythms and synchronise reproduction to the most optimal time of year [1, 2]. Melatonin acts directly on the pars tuberalis (PT) of the pituitary, regulating expression of thyrotropin (TSH) which then relays messages back to the hypothalamus to control reproductive circuits [3, 4]. In addition, a second local intra-pituitary circuit controls seasonal prolactin (PRL) release via a currently uncharacterised low molecular weight peptide(s) termed tuberalin(s) of PT origin [5–7]. Studies in birds identified the transcription factor Eya3 as the first molecular response activated by long photoperiods (LP) [8]. Using arrays and in situ hybridization studies, we show Eya3 as the strongest LP activated gene in sheep, revealing a common photoperiodic molecular response in birds and mammals. We also identified TAC1 (encoding the tachykinins Substance P and Neurokinin A; NKA) to be strongly activated by LP within the sheep PT. We show that these PRL secretagogues act on primary pituitary cells, and are thus candidates for the elusive PT-expressed “tuberalin” seasonal hormone regulator.

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Section: Resultsmentioning

confidence: 99%

Identification of Eya3 and TAC1 as Long-Day Signals in the Sheep Pituitary

et al. 2010

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“…Activation of MT1 melatonin receptors in the PT is known to inhibit adenylyl cyclase, and pharmacological studies in sheep have shown that melatonin impairs forskolin-induced hypersecretion of cAMP, with inhibition of prolactin from the PD through the reduction of a paracrine signal (44). However, although several compounds such as tachykinins, substance P, and neurokinin A are produced by the PT and can stimulate prolactin release (45)(46)(47), characterization of the chemical identity of that signal has been elusive. Here we show that the stimulatory effects of VEGF-A on prolactin were mimicked by conditioned media from PT cultures exposed to an NBS regimen of melatonin, and that these actions of PT media were blocked by a specific VEGF-A xxx a antibody, demonstrating that VEGF-A is a potential paracrine signal, and that melatonin-induced differential VEGF-A isoform production by the PT can regulate the seasonal production of prolactin and FSH.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function

Castle-Miller

Bates

Tortonese

2017

Proc. Natl. Acad. Sci. U.S.A.

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Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation, and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in day length (i.e., photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season (BS), angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication among the PT, PD, and brain. This also acts on VEGF receptor 2 (VEGFR2) expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the BS, melatonin releases antiangiogenic VEGF-Ab from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph (LT) VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of LTs, with up-regulation and down-regulation of gonadotrophin gene expression during the breeding and nonbreeding seasons, respectively. These results provide a mechanism by which melatonin can control pituitary function in a seasonal manner.

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“…Prolactinomas are the most common (20% of cases of pituitary apoplexy); this is related to the frequency of prolactinoma in the population and to their frequent hemorrhagic nature. Hyperprolactin can also result from stalk effect [88].…”

Section: Endocrine Function 71 Pituitary Hormone Excessmentioning

confidence: 99%

Pituitary Apoplexy

Jemel¹,

Alaya²,

Boubaker³

et al. 2019

Pituitary Diseases

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Pituitary apoplexy is a rare clinical emergency due to acute ischemic infarction or hemorrhage of the pituitary gland. As this disorder most often involves a pituitary adenoma, especially nonfunctioning tumors, the syndrome should be referred to as pituitary tumor apoplexy. The precise physiopathology is not completely clear. Although in most cases it occurs spontaneously, pituitary apoplexy can be precipitated by many risk factors. The main symptom is headache of sudden onset associated with visual disturbances, signs of meningeal irritation, and/or endocrine dysfunction. Corticotropic deficiency is a potentially life-threatening disorder. Magnetic resonance imaging is the most sensitive to confirm the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Earlier studies used to consider urgent decompression of the lesion surgically, but nowadays, more recent studies favor conservative management in selected patients (those without important visual acuity or field defects and with normal consciousness). This wait-and-see approach gives evidence of excellent outcomes in terms of oculomotor palsy, pituitary function, and subsequent tumor growth. Surgical decompression may be necessary in some cases. Once the acute phase is over, the patient should be reevaluated for hormonal deficiencies. Moreover, spontaneous remission of syndromes, such as acromegaly, may be caused by pituitary adenoma apoplexy.

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Rethinking the stalk effect: A new hypothesis explaining suprasellar tumor-induced hyperprolactinemia

Cited by 22 publications

References 10 publications

Identification of Eya3 and TAC1 as Long-Day Signals in the Sheep Pituitary

Identification of Eya3 and TAC1 as Long-Day Signals in the Sheep Pituitary

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function

Pituitary Apoplexy

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