Salsolinol is a Putative Endogenous Neuro‐intermediate Lobe Prolactin‐Releasing Factor

Abstract

The isolation and identification of a prolactin-releasing factor (PRF) from the neuro-intermediate lobe of the pituitary gland has been pursued for over a decade. Using high-pressure liquid chromatography with electrochemical detection (HPLC-ECD) and gas chromatography/mass spectrometry (GC/MS) (R)-salsolinol (SAL) (a dopamine-related stereo-specific tetrahydroisoquinoline) was found to be present in neuro-intermediate lobe as well as median eminence extracts of male, intact-, and ovariectomized female rats. Moreover, analysis of SAL concentrations in neuro-intermediate lobe revealed parallel increases with plasma prolactin in lactating rats exposed to a brief (10 min) suckling stimulus following 4-h separation. SAL appears to be a selective and potent stimulator of prolactin secretion in vivo and it was without effect on the secretion of other pituitary hormones. We have also found that SAL can elevate prolactin release, although to a lesser extent, in pituitary cell cultures as well as in hypophysectomized rats bearing anterior lobe transplants under the kidney capsule. Lack of interference of SAL with [3H]-spiperone binding to AP homogenates indicates that SAL does not act at the dopamine D2 receptor. Moreover, [3H]-SAL binds specifically to homogenate of AL as well as neuro-intermediate lobe obtained from lactating rats. Taken together, our data clearly suggest that SAL is synthesized in situ and this compound can play a role in the regulation of pituitary prolactin secretion.

Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release

“…This catechol isoquinoline may be synthesized directly from DA and acetaldehyde or indirectly, forming salsolinol-1-carboxylic acid and further to salsolinol (Naoi et al 1996(Naoi et al , 2002. Although not all enzymes of an indirect pathway of salsolinol synthesis are known, this compound and its metabolites can be detected in many areas of the brain that are also rich in DA (Toth et al 2001, Naoi et al 2002. In the current study, we have shown that salsolinol is present in the IN/ME of lactating ewes.…”

“…Our data did not show, however, a direct proof for salsolinol synthesis in these dopaminergic nuclei. So far, the presence of salsolinol in the ME has been shown in rats (Toth et al 2001). Musshoff et al (2000), studying human brain areas involved in the aetiology of alcoholism and Parkinsonism have also found salsolinol present in the hypothalamus.…”

“…This DA-originated compound, which is well known from its involvement in the progression of a disease characterized by dysfunctional dopaminergic neurons (Moser et al 1995, Antkiewicz-Michaluk 2002, was found to be present in neuro-intermediate lobe (NIL) as well as median eminence (ME) extracts of male, intact and ovariectomized female rats (Toth et al 2001). Salsolinol concentration has been shown to be elevated during situations when prolactin secretion is increased from the anterior lobe of the pituitary gland (Toth et al 2001), and salsolinol binds specifically with the pituitary cells of lactating rats (Toth et al 2002, Homicsko et al 2003.…”

Role of salsolinol in the regulation of pituitary prolactin and peripheral dopamine release

“…2a), namely at the terminal sites (ME and NIL) of the hypothalamic neuroendocrine DAerg (NEDA) neurons [25,33]. SAL can also be synthesized enzymatically by an already purified but still not sequenced enzyme, so called SAL-synthase [25,33]. As was remarked in the previous section, SAL is likely to act as an endogenous ME and NIL-derived PRF.…”

“…Lack of interference of SAL with [3H]-spiperone binding to AL homogenates [25] indicates that SAL does not act on the D2 DA receptors that are exclusively present on lactotropes. Moreover, [3H]-SAL can bind specifically to homogenate of AL obtained from lactating rats [48].…”