Effects of 5-day styrene inhalation on serum prolactin and dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats

Abstract

In several studies a hypersecretion of the pituitary hormone prolactin (PRL) in styrene-exposed workers has been described. This should cause reproductive problems like oligomenorrhea, secondary amenorrhea and reduced fertility [Arfini et al. (1987) J Occup Med 29:826-830, Bergamaschi et al. (1996) Neurotoxicology 17:753-760, Mutti and Smargiassi (1998) Toxicol Ind Health 14:311-323]. Secretion of PRL is tonically inhibited by the catecholamine dopamine (DA), which is released from hypothalamic neurons. It has been suggested that the activity of the enzyme dopamine-beta-hydroxylase (DBH) in the serum is a peripheral marker of central dopaminergic function. A slight reduction of such enzymatic activity was observed in styrene-exposed workers, which was associated with hypersecretion of PRL. To further investigate the putative effects of styrene on PRL release, male rats were exposed to styrene vapors (645, 2150 and 6450 mg/m(3)) for 6 h/day on 5 consecutive days. Animals were killed either directly following the last exposure (immediate group) or after a recovery period of 24 h (recovery group). Serum PRL and DA levels were measured by radioimmunoassay. Concentrations of catecholamines and their metabolites in the striatum and mediobasal hypothalamus (MBH) were determined by high performance liquid chromatography with electrochemical detection. Neither in the immediate nor in the recovery group were any statistically significant changes of serum PRL levels observed. Likewise, concentrations of catecholamines and their metabolites in the striatum and MBH remained unaffected. We conclude from these data that styrene, even at very high concentrations, has no adverse effects on the neuroendocrine mechanisms regulating PRL release and DA levels in the brain. With the limitations inherent in any animal model, we suggest that our data indicate that styrene also has no adverse neuroendocrine effects in humans.

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of styrene

“…Although the human data suggest effects of styrene on prolactin levels, two studies that evaluated prolactin levels in rats (Date et al, 2002;Jarry et al, 2002) failed to find any effect. The exposure levels used in these studies were 150-1500 ppm by inhalation for 5 days (Jarry et al, 2002) and 20 and 200 mg/kg bw/day s.c. for 7 days (Date et al, 2002).…”

“…The results support the authors' conclusions. Jarry et al (2002Jarry et al ( , 2004, support not indicated, evaluated serum hormones and prolactin-related central neurotransmitters in styrene-exposed male Wistar rats. Animals at about 13 weeks of age were exposed to styrene by inhalation at nominal concentrations of 0, 150, 500, or 1500 ppm (0, 645, 2150, or 6450 mg/m 3 ).…”

“…The exposure levels used in these studies were 150-1500 ppm by inhalation for 5 days (Jarry et al, 2002) and 20 and 200 mg/kg bw/day s.c. for 7 days (Date et al, 2002). The Jarry et al (2002) study also found no effect of styrene exposure on hypothalamic dopamine levels. This lack of effect, combined with a lack of any indication from the multi-generation or chronic studies of a perturbation in prolactin function, is inconsistent with the human data.…”

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

“…Details of the exposure procedure have been reported previously (Jarry et al, 2002). In brief, to adapt the rats to the experimental conditions, they were kept individually in wire cages placed in a glass-steel inhalation chamber with a volume of 1.4 m 3 .…”

“…Therefore, we determined these parameters in male rats which have inhaled styrene at 3 different doses over a period of 5 days. The effects of these treatments on prolactin levels and brain dopamine concentrations have been reported in the first part of this study (Jarry et al, 2002). Male rats were chosen because the vast majority of studies on putative neurotoxic effects of styrene were performed with male animals (Ladefoged et al, 1998;Takao et al, 2000;Chakrabarti, 2000) and because it has been shown that in male rats with low LH and T levels, GABAergic neurotransmission in the MBH is increased (Leonhardt et al, 1999).…”