J. Endocrinol. Invest. 15: 497-499,1992
Prolactin bioassay and hyperprolactinemia C.A. Peabody*, P.N. Schultz**, MD. Warner***, I.G. Worsley****, H.G. Friesen****, and N.A. Samaan** *Department of Psychiatry, University of Texas Medical School, **University of Texas, MD Anderson Cancer Center, USA, ***Department of Psychiatry, Baylor Medical School, and ****Department of Physiology, University of Manitoba, Canada ABSTRACT. The Nb2 rat lymphoma bioassay (SA) for prolactin (PRL) was performed in 26 subjects with hyperprolactinemia, 17 of whom had radiologic evidence of a pituitary adenoma. All subjects were treated with the long acting dopamine agonist CV
205-502. The radioimmunoassay (RIA) PRL significantly decreased with treatment but the SA/RIA PRL remained essentially the same, indicating that the relative bioactivity was unaffected.
INTRODUCTION
tahydrobenzoly[g]guinolone, Sandoz Pharmaceuticals) was 75 Ilg/day after a 6 weeks medication-free period. The maximum dose was 375 Ilg/day and the average dose was 133 Ilg/day. All doses were given once at bedtime with a snack. Treatment duration ranged from 2 months to 19 months. One subject had a diagnosis of multiple endocrine neoplasia, type I. Only 2 subjects were on medication, one was on cephalexin (Keflex) and the other was on Spironolactone (Aldactone) and thyroxine (Synthroid). The mean age of the group was 36 yr (range 13-53). Thirteen subjects from the current study are included in the Vance et al. report (2). The study was approved by the internal review board at MD Anderson Hospital. All subjects gave written informed consent.
It is well accepted that multiple molecular forms of immunoreactive human prolactin (PRL) exist with differences in molecular weight and biological activity. This prolactin heterogeneity with differing biological activity may in part explain why radioimmunoassay (RIA) measurements do not always correlate with clinical findings. An indirect method for assessing a change in the molecular forms is via the bioactivity. Until 1980 when the Nb2 rat lymphoma cell bioassay (BA) for PRL was described, there was no practical and sensitive method for the assessment of PRL bioactivity in humans (1). In the present study we measured the ratio of the Nb2 BA to RIA PRL in patients with hyperprolactinemia. Levels were determined both before and after treatment with the long acting dopamine agonist CV 205-502.
Design and Assays All subjects' blood was drawn in a nonresting, nonfasting, state. Serum prolactins were drawn monthly for up to 19 months. Two samples were chosen for PRL BA: one at baseline and the first sample in which prolactin was less than 30 ng/ml or if this never occurred then the lowest of the posttreatment values. All serum and culture media samples were kept frozen at -20 until assayed. RIA PRL (3, 4) and GH (5, 6) levels were determined by radioimmunoassay. Normal values for RIA PRL are ~ 18 ng/ml and RIA GH values are ~ 10 ng/ml. The RIAs on all subjects were performed in the same assay. The Nb2 node lymphoma bioassay was performed as previously described (1).
MATERIALS AND METHODS Subjects Twenty-six subjects (23 women, 3 men) with a serum prolactin of at least 25 ng/ml participated in this study. All women had either amenorrhea or galactorrhea. One man had galactorrhea and two men had visual field defects. Growth hormone (GH) was normal in all subjects. A pituitary adenoma was confirmed by either a CT or MRI scan in 17 subjects. Thirteen subjects had a history of transsphenoidal excision of an adenoma but had persistent hyperprolactinemia. The initial dose of CV 205-502 (oc-
RESULTS
Key-words: Prolactin, bioassay, CV205-502, hyperprolactinemia. Correspondence: CeCilia A. Peabody MO, Harris County Psychiatric Center, 2800 MacGregor Way, Houston, Texas 77021, USA
A paired ttest was used to determine differences in RIA PRL, BA PRL and BA/RIA PRL before and after
Received December 12, 1991; accepted May 7,1992.
497
G.A. Peabody, PN. Schultz, MD. Warner, et al.
treatment (Table 1). All correlations were performed by the Spearman rank method. Correlations were noted between baseline BA and baseline RIA PRL (r=0.96, n=26, p
Prolactin bioassay and hyperprolactinemia C.A. Peabody*, P.N. Schultz**, MD. Warner***, I.G. Worsley****, H.G. Friesen****, and N.A. Samaan** *Department of Psychiatry, University of Texas Medical School, **University of Texas, MD Anderson Cancer Center, USA, ***Department of Psychiatry, Baylor Medical School, and ****Department of Physiology, University of Manitoba, Canada ABSTRACT. The Nb2 rat lymphoma bioassay (SA) for prolactin (PRL) was performed in 26 subjects with hyperprolactinemia, 17 of whom had radiologic evidence of a pituitary adenoma. All subjects were treated with the long acting dopamine agonist CV
205-502. The radioimmunoassay (RIA) PRL significantly decreased with treatment but the SA/RIA PRL remained essentially the same, indicating that the relative bioactivity was unaffected.
INTRODUCTION
tahydrobenzoly[g]guinolone, Sandoz Pharmaceuticals) was 75 Ilg/day after a 6 weeks medication-free period. The maximum dose was 375 Ilg/day and the average dose was 133 Ilg/day. All doses were given once at bedtime with a snack. Treatment duration ranged from 2 months to 19 months. One subject had a diagnosis of multiple endocrine neoplasia, type I. Only 2 subjects were on medication, one was on cephalexin (Keflex) and the other was on Spironolactone (Aldactone) and thyroxine (Synthroid). The mean age of the group was 36 yr (range 13-53). Thirteen subjects from the current study are included in the Vance et al. report (2). The study was approved by the internal review board at MD Anderson Hospital. All subjects gave written informed consent.
It is well accepted that multiple molecular forms of immunoreactive human prolactin (PRL) exist with differences in molecular weight and biological activity. This prolactin heterogeneity with differing biological activity may in part explain why radioimmunoassay (RIA) measurements do not always correlate with clinical findings. An indirect method for assessing a change in the molecular forms is via the bioactivity. Until 1980 when the Nb2 rat lymphoma cell bioassay (BA) for PRL was described, there was no practical and sensitive method for the assessment of PRL bioactivity in humans (1). In the present study we measured the ratio of the Nb2 BA to RIA PRL in patients with hyperprolactinemia. Levels were determined both before and after treatment with the long acting dopamine agonist CV 205-502.
Design and Assays All subjects' blood was drawn in a nonresting, nonfasting, state. Serum prolactins were drawn monthly for up to 19 months. Two samples were chosen for PRL BA: one at baseline and the first sample in which prolactin was less than 30 ng/ml or if this never occurred then the lowest of the posttreatment values. All serum and culture media samples were kept frozen at -20 until assayed. RIA PRL (3, 4) and GH (5, 6) levels were determined by radioimmunoassay. Normal values for RIA PRL are ~ 18 ng/ml and RIA GH values are ~ 10 ng/ml. The RIAs on all subjects were performed in the same assay. The Nb2 node lymphoma bioassay was performed as previously described (1).
MATERIALS AND METHODS Subjects Twenty-six subjects (23 women, 3 men) with a serum prolactin of at least 25 ng/ml participated in this study. All women had either amenorrhea or galactorrhea. One man had galactorrhea and two men had visual field defects. Growth hormone (GH) was normal in all subjects. A pituitary adenoma was confirmed by either a CT or MRI scan in 17 subjects. Thirteen subjects had a history of transsphenoidal excision of an adenoma but had persistent hyperprolactinemia. The initial dose of CV 205-502 (oc-
RESULTS
Key-words: Prolactin, bioassay, CV205-502, hyperprolactinemia. Correspondence: CeCilia A. Peabody MO, Harris County Psychiatric Center, 2800 MacGregor Way, Houston, Texas 77021, USA
A paired ttest was used to determine differences in RIA PRL, BA PRL and BA/RIA PRL before and after
Received December 12, 1991; accepted May 7,1992.
497
G.A. Peabody, PN. Schultz, MD. Warner, et al.
treatment (Table 1). All correlations were performed by the Spearman rank method. Correlations were noted between baseline BA and baseline RIA PRL (r=0.96, n=26, p
