Metabolic clearance and production rates of prolactin in man.

Abstract

A B S T R A C T Metabolic clearance rates (MCR) and production rates (PR) of prolactin (PRL) have been determined by the constant infusion to equilibrium technique in 11 normal subjects, 6 patients with hyperthyroidism, 4 patients with hypothyroidism, and 9 patients with hyperprolactinemia. PRL MCR was also determined in four patients during dopamine infusion. Mean PRL MCR was 46±1 ml/min per m2 in women and 44±3 ml/min per m2 in men, and was significantly correlated with body mass (r = 0.84, P < 0.001). In contrast with controls, PRL MCR was higher in hyperthyroidism (MCR = 52±8 ml/min per mi2, P < 0.05), was slightly lower in hypothyroidism (MCR = 38+10 ml/min per m2, P = NS), and was significantly correlated with serum thyroxine (r = 0.46, P < 0.02). PRL MCR was lower than controls in hyperprolactinemia (MCR = 40+5 mllmin per i2, P <0.01) and was inversely correlated with serum PRL (r = -0.72, P < 0.001). PRL MCR was not significantly changed by dopamine infusion.Mean PRL PR for women and men was 211±74 and 187±44 ,ug/d per m2, respectively (P = NS). In hyperthyroidism the PRL PR was elevated (PR = 335±68 ,ug/d per m2, P < 0.02), but in hypothyroidism the increase (PR = 233±159 ,tg/d per m2) was not significant. In hyperprolactinemia the PRL PR was extremely high (PR = 31,000±29,000 ,ig/d per m2). Dopamine infusion decreased PRL PR from 270 to 66,ug/d per m2 indicating that its effect was on pituitary PRL secretion and not PRL metabolism.To evaluate possible circulating PRL heterogeneity that might arise during infusion, gel filtration of infusate and serum obtained during the MCR procedure was performed. Labeled monomeric PRL (peak III, Kav (partition coefficient) = 0.4) was partially A preliminary account of this work was presented at the 61st Annual Meeting of the Endocrine Society, Anaheim, Calif., 13-15 June, 1979. Received for publication 29 January 1979 and in revised form 9 August 1979. converted to two larger forms (peaks I and II) in vivo. Peak I (Kav = 0) was 30-40% immunoprecipitable, although peak II (Kav = 0.2) was not immunoprecipitable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak I resulted in .90% conversion to peak III and restoration of full immunoactivity. Thus, peak

A dose rising study of the safety and effects on serum prolactin of SK&F 101468, a novel dopamine D2‐receptor agonist.

“…SK&F 101468 is, however, clearly very potent with an effect evident at doses as low as 80 ,ug. In general an effect on prolactin was evident within about forty five minutes of dosing which approximates to the serum half life of prolactin (Cooper et al, 1979).…”

“…The short plasma half-life of prolactin (approximately 40 min) and its fast metabolic clearance (Cooper et al, 1979) therefore make it a valuable marker for confirming the pharmacological effect of dopamine agonists at D2-receptors in humans.…”

Postictal Prolactin Elevations in Rats

“…Some supporting evidence for this is seen in the lack of fall in postictal prolactin levels dur ing the period of observation. This steady level suggests the possibility that atropine-treated postictal rats may have released prolactin in response to perceived postictal non-seizural stresses, balancing against the rate of meta bolic disappearance [Cooper et al, 1979]. Since postictal levels of atropinized rats do not exceed those following irritation only and are likely lower than postictal levels in drug-free rats, there is no clear evidence of a seizure-spe cific prolactin rise in rats receiving atropine pretreatment.…”

Suppressed plasma prolactin response to thyrotropin-releasing hormone in hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects

“…However, the increase in PRL metabolic clearance rate was considered minor compared with that in PRL production rate that is also encountered in hyperthyroidism (Cooper et al 1979). …”