Virus-induced alterations in homeostasis: alteration in differentiated functions of infected cells in vivo.

The noncytopathic lymphocytic choriomeningitis virus displays a tropism for the anterior lobe of the murine pituitary gland. Virus replicates in cells that make growth hormone. This results in a diminished synthesis of growth hormone with a concomitant clinical picture of retarded growth and hypoglycemia. However, there is no morphologic evidence of either cell necrosis or inflammation in the anterior lobe of the pituitary. Hence, during infection in vivo, a noncytopathic virus may turn off the "differentiation" or "luxury" function of a cell while not killing that cell (loss of vital function). This is turn can disrupt homeostasis and cause disease. This model illustrates a novel way whereby viruses may cause disease.

Mammary tumorigenesis in chemical carcinogen-treated mice. VII. Prolactin and progesterone levels in BALB/c mice.

PIP: Pituitary and serum levels of prolactin (PRL) and serum levels of progesterone (P) were determined by polyacrylamide gel electrophoresis and radioimmunoassays in BALB/c female mice, 15-17 or 44 weeks old, treated with chemical carcinogens. Neither 1.5 mg 3-methylcholanthrene (MCA) nor 1.5-6 mg 7,12-dimethylbenz(a)anthracene (DMBA) markedly altered pituitary or serum levels of PRL in the younger mice, though DMBA increased the total pituitary content of PRL by about 33% in the 44-week-old mice. However, this increase was not correlated with the incidence of mammary tumors in the group or individuals. MCA increased serum P levels by about 22% within 50 days of the last treatment. This increase was attributable to higher serum levels of P during the diestrous and proestrous phases of the cycle. Adrenalectomy reduced serum P levels by about 60%, wheras ovariectomy had no effect. Serum P levels in 44-week-old rats were not affected by DMBA. The results fail to support the notion that MCA and DMBA promote murine mammary tumorigenesis by increasing pituitary and serum prolactin concentrations.^ieng

Prolactin variants.

Prolactin (PRL) is one of the most versatile hormones of the pituitary in terms of biologic actions, but how a single molecule is able to evoke so many different responses in the organism is not known. Research in recent years has uncovered a surprising degree of structural polymorphism for PRL, the different forms having variable biopotencies. Such findings lend credence to the hypothesis that the molecular heterogeneity of PRL is one of the mechanisms for creating diversity in the biologic actions of this hormone.

Molecular size variants of prolactin and growth hormone in mouse serum: strain differences and alterations of concentrations by physiological and pharmacological stimuli.

Molecular size heterogeneities of PRL and GH in mice of the high mammary tumor C3H/St strain and low mammary tumor C57BL/St strain were compared under different physiological states. At least three size variants, the big (void volume), the intermediate (dimeric), and the little (monomeric) forms, of both hormones were detected in the sera and pituitary extracts. The big and the little forms of each hormone were the most prevalent; the intermediate form was detectable in only a few instances. In both strains, only big PRL was found in the sera of 15-day-old mice of both sexes. At 80 days of age, males of both strains still had only big PRL, but females of the low tumor C57BL/St strain now possessed only the little PRL, whereas those of the high tumor C3H/St strain continued to have mainly the big PRL. This pattern held true during late pregnancy. It is probable that this strain difference in the molecular size profile of PRL in adult females may be related to their incidence of mammary tumors. Lactation, nursing, perphenazine injection, estradiol benzoate treatment, all stimuli that enhance PRL secretion, increased the proportion of little PRL in sera and abolished the strain difference existing in the nonlactating state. Progesterone also increased the proportion of little PRL in female mice but not in males. Testosterone had no effect in either sex. Both the big and little forms of PRL were found in pituitary extracts, the big form comprising less than 5% in most animals except the 15-day-old mice, in which it constituted about 10% in both sexes. A small amount (approximately 2%) of intermediate PRL was also found when the pituitary extracts were chromatographed on a longer column. The pituitary patterns were not changed appreciably by any of the stimuli tested. These results suggest that little PRL may be the form that is predominantly secreted under most conditions. GH was present in the big and little forms in the sera of 15-day-old mice of both sexes, the little form being the major constituent. At 80 days of age, the pattern changed. Now the big GH was the greater constituent in mice of both sexes, with no appreciable difference between the two strains. During late pregnancy, serum GH levels increased to high levels in the C3H/St strain, yet most immunoreactive GH was present in the big form in mice of both strains. Lactation, nursing, or estradiol benzoate treatment produced no marked changes in the GH profile, but progesterone, testosterone, or perphenazine injections seemed to increase the proportion of the little GH in serum. Pituitary extracts from pregnant mice or others showed no demonstrable changes in the proportions of the different GH forms that correlated with the patterns found in serum. The results suggest that the larger forms of PRL and GH are natural entities in the mouse plasma, resulting mostly from postsecretional transformations in systemic circulatin...

Identification of a less immunoreactive form of prolactin in the rat pituitary.

Disc electrophoretic analysis of prolactin (PRL) in the rat pituitary is usually performed using a 7.5% concentration of acrylamide gel. Re-electrophoresis of the eluate of the PRL band from such a gel on polyacrylamides of serially increasing concentrations revealed that the PRL band of 7.5% gel actually contains at least two additional proteins. One of these, whose apparent mol. wt. is 31,000, has significant pigeon crop-sac stimulating activity but very little or no cross-reactivity in a RIA for rat PRL. It also has a rapid turnover rate in short-term in vitro incubations. This newly-found protein seems to be a nonimmunoreactive molecular variant of rat PRL.

Estrogen in high doses inhibits perphenazine-induced prolactin release.

We investigated the effects of high doses of estrogen on the basal and stimulated secretion of PRL. Daily administration of 0.1 micrograms estradiol benzoate to female mice for 4 weeks significantly increased the amplitude of PRL release induced by perphenazine. A dose of 1.0 micrograms had no stimulatory effect, while doses of 10, 20, and 50 micrograms completely prevented the release of PRL in response to perphenazine. The rise in basal serum PRL concentrations seen at lower doses of estradiol benzoate was also minimized with 20- and 50-micrigrams doses. At the same time, PRL concentrations within the pituitary gland as well as pituitary weight consistently increased in response to all high doses of estradiol benzoate tested, although the increment at the highest dose (50 micrograms) was somewhat smaller. These results suggest that prolonged administration of estrogen in large amounts may be detrimental to the natural, acute release of PRL. We postulate that this effect may account, in part, for the observed mammostatic and antigalactic effects of high doses of estrogen.

Effect on growth of prolactin deficiency induced in infant mice.

The effect of lowering PRL levels in blood during early infancy on subsequent growth and development was studied in mice. PRL was reduced by injecting either an antiserum raised against homologous PRL or a PRL-inhibiting drug, 2-chloro-6-methylergoline-8 beta-acetonitrile methanesulfonate (ergoline), into 4-day-old mice for a period of 4 or 5 days. Both the anti-PRL serum and ergoline rapidly killed some of the injected animals, but the effect of anti-PRL serum was much more severe than that of ergoline (39% vs. 8.7% mortality during the period of injection). Similar administration of an antiserum against mouse GH or the GH-inhibiting peptide somatostatin did not cause a significant number of deaths. The deaths from the anti-PRL serum largely ceased when the antiserum was neutralized with rat PRL (NIH-RP-1) before injection. The gain in body weight of baby mice was markedly retarded within 24 h of injecting anti-PRL serum and ergoline, in contrast to the anti-GH serum and somatostatin injections, which took 3--4 days to inhibit growth perceptibly. The anti-PRL serum, despite having only one eighth the titer of anti-GH serum, was by far the most effective of the two antisera in diminishing tibial epiphyseal cartilage width as well as weights of pituitary glands, testes, and adrenals and retarding sexual maturity. The more severe and generalized developmental abnormalities and the incidence of mortality as a result of anti-PRL serum administration suggest that PRL in mice may be involved in the maintenance of some vital function during infancy.

Structural and immunologic evidence for a small molecular weight ("21K") variant of prolactin.

The mol wt (Mr) of intact murine PRL is approximately 23,000. Immunoblotting analysis shows a 21,000 Mr band in fresh rat and mouse pituitary extracts that cross-reacts strongly with PRL antibodies. The band becomes markedly altered by stimuli known to influence PRL secretion, such as nursing, estradiol benzoate, and perphenazine. By two-dimensional electrophoresis, it splits into at least three components, two of which have more acidic pI than PRL. The tyrosine peptide maps of the three proteins resemble that of PRL. These results indicate that the 21,000 Mr band consists of a cluster of proteins that are structural variants of PRL, raising the possibility that these variants result from alternative splicing of the PRL gene transcript.

A cleaved form of prolactin in the mouse pituitary gland: identification and comparison of in vitro synthesis and release in strains with high and low incidences of mammary tumors.

A form of rat PRL with a clip in its large disulfide loop, the so-called cleaved PRL, has been reported to have a greater mammogenic activity than the intact molecule. This study was undertaken to investigate the presence of cleaved PRL in the mouse pituitary gland with the purpose of correlating its concentrations with the incidence of mammary tumors. We could identify this molecule in the mouse pituitary by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, although its concentration was not high enough for ready detection in crude extracts of pituitary tissues. Cleaved mouse PRL and its 16 K and 8 K fragments cross-reacted with antibodies to the intact molecule and, thus, cannot be differentiated from the latter by RIA. When pituitaries were incubated for 6 h with 14C-labeled amino acids, cleaved PRL from the pituitaries of male mice incorporated more radioactive amino acids than the corresponding molecules from female mice. However, treatments such as ovariectomy, ovariectomy plus estradiol benzoate, perphenazine, and 2-Br-alpha-ergocryptine affected the concentration of labeled cleaved PRL in the same manner as they did that of the intact molecule. The ratio of labeled cleaved PRL to the labeled intact molecule in mice with a high incidence of mammary tumors (C3H/St) was not much different from that in mice with a low incidence (C57BL/6J) in pituitary plus medium. However, this ratio was slightly but consistently higher in medium from the C3H/St strain, raising the interesting question whether such a preponderance prevails in the circulation of this and other mammary tumor-prone strains as well.

Prolactin and growth hormone secretion in chemically induced and genetically obese mice.

Experiments were performed to determine PRL and GH concentrations in mice rendered obese by chemical means and to compare these concentrations with those of mice obese as a result of genetic mutation. Basal levels of serum PRL and GH were generally lower in gold thioglucose (GTG) and bipiperidyl mustard (BPM)-treated obese mice compared with lean controls. In the pituitary gland, the hormonal changes varied from lower or unchanged levels of PRL and GH shortly after drug injection to very high concentrations of PRL (but not of GH) a year later. However, when the mice were challenged with perphenazine, a drug that causes prompt release of PRL, GTG and BPM-obese mice released 2-5 times as much PRL as did lean controls, suggesting an impairment in the hypothalamic control of PRL secretion in GTG/BPM-obese mice. Basal levels of PRL and GH in genetically obese (ob/ob) mice of both sexes were also lower than those in their lean relatives (?/+). This was true for both serum and pituitary concentrations of the two hormones, the only exception being pituitary GH concentrations in females which were higher than or equal to those of controls. However, unlike GTG and BPM-obese mice, genetically obese mice released very little PRL compared with their lean relatives when stimulated with perphenazine, which suggested an insufficiency of pituitary function in ob/ob mice. The results demonstrate abnormalities in the secretion of PRL and GH in obese mice of both types.

Age-correlated and ovary-dependent changes in relationships between plasma estradiol and luteinizing hormone, prolactin, and growth hormone in female C57BL/6J mice.

Impairments in the estradiol (E2)-induced surge of LH occur as aging female rodents lose reproductive cycles. These and other impairments can be substantially attenuated by ovariectomy of the young adult. In female rats, plasma PRL tends to increase with age, whereas in male rats, GH tends to decrease; PRL is regulated by E2, whereas GH is probably not. To determine if age-correlated neuroendocrine impairments are accompanied by altered neuroendocrine sensitivity to E2, the relationships among plasma E2, LH, PRL, and GH were assessed in 6- and 12-month-old cycling and 18-month-old acyclic female C57BL/6J mice given E2 implants. An additional 18-month-old group, ovariectomized at 6 months of age, was examined to determine if age-correlated changes in sensitivity to E2 are ovary dependent. One week after ovariectomy, mice were given different sized E2 implants which generated a physiological range of plasma E2. Three weeks after implantation, plasma E2 correlated positively with implant size, uterine weight, and PRL, but correlated negatively with LH in each age group; age did not affect plasma E2 levels. The suppression of LH by E2 decreased progressively with age. Conversely, the elevation of PRL by E2 increased with age. These effects of age were largely prevented by ovariectomy at 6 months of age. Plasma GH decreased slightly with age, but was not significantly affected by E2; old mice ovariectomized when young had lower GH levels than previously intact old mice. GH also correlated positively with LH in all age groups. We conclude that neuroendocrine responses to E2 are altered with age even before estrous cycles are lost. Sensitivity to E2 may either increase or decrease, depending on the function. These effects of age can be attenuated by prolonged ovariectomy. Thus, chronic exposure to ovarian E2 during normal reproductive cycles may alter neuroendocrine sensitivity to E2, which may lead to age-correlated impairments in reproductive function.

Cholera toxin treatment increases in vivo growth and development of the mouse mammary gland.

Daily sc injections of cholera toxin (CT; 0.1 micrograms/day), a stimulator of adenylate cyclase activity, into intact female BALB/c mice for 20 days significantly (P less than 0.05) increased mammary gland development scores from 2.0 +/- 0.1 in controls to 3.6 +/- 0.2 in CT-treated mice. Concurrent administration of 17 beta-estradiol (E; 1.0 microgram/day) and progesterone (P; 1.0 mg/day) resulted in development scores of 4.1 +/- 0.1 and 5.2 +/- 0.1 in E/P and E/P + CT treatment groups, respectively (P less than 0.05). If mice were ovariectomized before CT injection, the response to CT alone was abolished (development scores of 2.0 +/- 0.1 and 1.9 +/- 0.1 in controls and CT-treated mice, respectively). However, E/P restored the response to CT (scores of 3.2 +/- 0.2 for E/P and 4.0 +/- 0.1 for E/P + CT; P less than 0.05) in ovariectomized mice. CT significantly (P less than 0.05) increased mammary dry fat-free tissue weight from 2.89 +/- 0.41 mg (controls) to 3.78 +/- 0.37 mg (CT-treated) and from 4.03 +/- 0.59 mg (E/P-treated) to 5.42 +/- 0.91 mg (E/P + CT). Similarly, CT treatment increased mammary DNA from 138.7 +/- 11.7 micrograms (controls) to 162.8 +/- 14.4 micrograms (CT) and from 178.5 +/- 12.6 to 233.9 +/- 28.0 micrograms in the presence of E/P (P less than 0.05). Furthermore, CT was found to be mammogenic in hypophysectomized mice treated with E (1.0 microgram/day), P (1.0 mg/day), deoxycorticosterone acetate (0.5 mg/day), T4 (0.2 microgram/ml drinking water), and glucose (50 mg/ml drinking water), i.e. mammary gland development scores were 1.5 +/- 0.1 in mice treated with the above regimen and 3.1 +/- 0.1 in mice treated with the above regimen plus CT for 14 days (P less than 0.05). These results provide clear evidence, heretofore unreported, that systemic CT treatment increases mammary gland development and growth in female mice. The mammogenic effects of CT are observed in intact female mice with or without exogenous E/P, in ovariectomized mice treated with E/P, and in hypophysectomized mice treated with E/P, deoxycortisone acetate, and T4.

Prolactin status of hereditary dwarf mice.

Snell (dw/dw) and Ames (df/df) dwarf mice of both sexes were evaluated for immunoassayable PRL in plasma and for the presence of PRL-containing cells in the hypophysis. Regardless of the method of blood collection (decapitation or cardiac or orbital puncture), minimal concentrations of PRL were detected in the plasma of hereditary dwarf mice. PRL secretion was not augmented in Snell or Ames female dwarfs after treatment with perphenazine or estradiol benzoate, stimuli which greatly increased PRL release in normal female littermates. Comparison of PRL levels in dwarf animals (dw/dw or df/df) using two different homologous RIAs substantiated the observation that male and female dwarfs are PRL deficient. Mammotropes, readily detectable in the pituitary glands of all normal siblings of Snell and Ames mice, were absent from the dwarf mouse hypophysis, which was markedly reduced in size. The lack of PRL-containing cells in the dwarf mouse pituitary may explain why peripheral PRL levels in this animal are below those measured in hypophysectomized mice.

Prolactin and growth hormone levels in different inbred strains of mice: patterns in association with estrous cycle, time of day, and perphenazine stimulation.

These experiments were designed to compare prolactin (PRL) and growth hormone (GH) secretion in strains of mice with varying incidences of mammary tumors. In addition to the basal levels, PRL concentrations were compared after stimulation with perphenazine. Although pituitary concentrations of PRL and pituitary serum concentrations of GH appeared to be generally higher in strains with high incidence of mammary tumors, basal PRL levels in single decapitate serum samples seemed to have little correlation with the incidence of mammary tumors in different strains. However, PRL concentrations in sera after perphenazine injection followed a pattern characteristic of the mammary tumor incidence rate of the strain: C3H/St and CBA/St--the two high-incidence strains--had lower levels of PRL; C57BL/St and BALB/cST--the two low-incidence strains--had higher levels; and DBA/2St--the medium-incidence strain--had an intermediate level. PRL contents of the pituitary glands were depleted virtually equally in all strains except the BALB/cSt. These results suggested that the rate of metabolism of PRL in strains with high incidence of mammary tumors may be faster than in those with low incidences. Perphenazine had no influence on GH secretion in most mice. The strain-specific differences in PRL and GH concentrations were usually present even during cyclical and diurnal fluctuations. Serum PRL and GH levels were generally higher during the follicular phase and lower during the luteal phase of the estrous cycle in both C3H/St and C57BL/St strains. There were signs of episodic secretion of PRL together with evidences of circadian periodicity in the secretion of PRL and GH in mice of both strains. The levels of GH were usually high during the morning hours of those of PRL high during the evening hours. The data show a high degree of specificity in the secretion of PRL and GH im mice of different inbred strains, and it is possible that these strain-specific differences may be an important factor in the development of mammary tumors.

Control of prolactin and growth hormone secretion in mice by obesity.

Prolactin (PRL) and growth hormone (GH) secretions in mice rendered obese by the administration of gold thioglucose (GTG) are abnormal. The objective of the present experiments was to determine whether the effects were related to the drug or to the resultant obesity. Perphenazine-induced PRL release in normal mice and in GTG-injected non-obese mice was compared to that of GTG-injected obese mice after the initial development of obesity, after body weight reduction by diet control and after the resumption of obesity by ad lib. feeding. The GTG-injected mice which did not become obese had greater (50%) than normal levels of serum PRL following perphenazine stimulation in 2 of 3 experiments. This suggested that the injection of GTG directly affected the control mechanism for PRL secretion, but that the abnormal PRL secretion was probably not the cause of obesity that develops after GTG treatment. Perphenazine-induced PRL levels in mice rendered obese with GTG were much greater (2-3 times higher than normal). However, the unusually high levels of PRL were totally abolished when the body weights of these mice were brought down to normal by dietary restriction. Conversely, when obesity was permitted to recur by giving the mice free access to food, PRL levels reverted back to the original obese pattern. The concentrations of GH were usually lower than normal in GTG-obese mice, and these levels were also more often associated with the development of obesity than with the injection of GTG. The data show a marked influence of obesity on the control of PRL and GH secretions in the mouse.

Serum growth hormone and prolactin during and after the development of the obese-hyperglycemic syndrome in mice.

Mice with the recessively inherited obese-hyperglycemic syndrome (ob/ob) and their nonobese litter mates were studied over a 26-week period. The body weights and serum glucose levels of ob/ob mice began to rise markedly at 5-6 weeks of age and remained elevated throughout the period of study. Obese mice were significantly heavier (P less than .001) and had higher serum glucose levels (P less than .001) than lean mice, but obese mice had variably lower serum growth hormone (GH) and prolactin (PRL) levels (P less than .001) than lean litter mate controls after 4-5 weeks of life. A 24 h rhythm study performed on 15-week-old mice revealed a relatively unaltered but attenuated pattern of GH and PRL secretion in ob/ob mice. During and after the development of the obese-hyperglycemic syndrome, the low levels of these two hormones probably indicates an altered hypothalamic regulation of pituitary function.

Changes in the glycosylated and nonglycosylated forms of prolactin and growth hormone in lean and obese pigs during pregnancy.

The concentrations of glycosylated (G-PRL) and nonglycosylated (non-G-PRL) forms of PRL and GH were measured during pregnancy in pigs of lean and obese (high backfat thickness) lines. Pregnant sows of the two genetic lines were killed, in groups of five to eight, at 60, 75, 90, and 105 days of gestation, and their pituitary glands and plasma were analyzed for the two hormones by immunoblotting, lectin-binding, and RIA techniques. In both lean and obese pigs, pituitary concentrations of G-PRL and non-G-PRL increased with advance in pregnancy, but there were no significant changes in either form of pituitary GH. Plasma concentrations of radioimmunoassayable PRL also increased with advance in pregnancy, with no consistent changes in serum GH concentrations. The dominant PRL constituent in plasma during the second half of pregnancy was G-PRL, and its concentration either increased or remained constant with advance in pregnancy. In contrast, plasma non-G-PRL concentrations decreased with advance in pregnancy in both lines of pigs, resulting in a steady rise in the plasma G-PRL/PRL ratio toward term. Compared to lean pigs, obese pigs had less radioimmunoassayable PRL and GH in their plasma and less GH (glycosylated as well as nonglycosylated) in their pituitary glands, but obese pigs had more G-PRL in their pituitary glands than lean pigs, and their plasma G-PRL levels tended to be higher and non-G-PRL levels lower than those of lean pigs. Pituitary concentrations of non-G-PRL in the two lines of pigs were similar. Overall, the results show a preponderance of G-PRL over non-G-PRL in the plasma of pregnant sows, with a preferential secretion of the glycosylated form during the latter half of pregnancy. Furthermore, they indicate a prevalence of higher G-PRL/PRL ratios in the pituitary glands of obese than lean pigs. These findings raise the possibility of a functional role for the glycosylated variant of PRL in the initiation and/or maintenance of events associated with pregnancy and obesity in the pig.

Glycosylated human prolactin.

A glycosylated form of human PRL (G-hPRL) was isolated from pituitary glands. The glycoprotein was separated from the major form of PRL on columns of lentil lectin-Sepharose 4B. The major form of PRL did not bind to the lentil lectin, whereas the glycosylated modification did and could be eluted with methyl-alpha-D-mannopyranoside. By gel electrophoresis in sodium dodecyl sulfate, a mol wt of 25,000 was estimated for the glycosylated PRL. The mol wt of hPRL is 23,000. In a RIA for hPRL, the glycosylated hormone was about one third as reactive as the principal form. Since there is only one Asn-X-Ser(Thr) sequence in hPRL, the asparagine at position 31 is the likely point of N-linked glycosylation.

Enumeration of lactotropes and somatotropes among male and female pituitary cells in culture: evidence in favor of a mammosomatotrope subpopulation in the rat.

The hemolytic plaque assay technique can be used to detect specific hormone release from single pituitary cells. Using antisera raised against murine GH or rat PRL, we have enumerated the active lactotropes and somatotropes from male and female rat pituitary glands. These studies reveal sex-related differences in the number of cells exporting GH and PRL among anterior pituitary cells in culture. In the presence of human GH-releasing factor (hGRF), the mean percentage of GH cells was 53% in males and 30% in females (P less than 0.005). The mean percentage of PRL cells was 15% in males and 39% in females (P less than 0.008). These values were not significantly altered when hGRF was omitted. The sum of GH and PRL cells identified in separate plaque assays significantly exceeds the number obtained when GH and PRL cells were determined concurrently with a simultaneous plaque assay for both hormones. This difference is dependent on the presence of hGRF, since there was no difference when hGRF was omitted. These data identify the mammosomatotrope in numbers lower than previous reports. By this approach, the mammosomatotrope subpopulation numbers about 5% of all cells in culture. In summary, we demonstrate a sex-related difference in the number of cells exporting GH or PRL among pituitary cells in culture. This difference corresponds with and may underly sex-related differences in the responsiveness of GH and PRL secretion from the pituitary gland. Furthermore, a minor subpopulation of normal pituitary cells appears capable of simultaneous secretion of both GH and PRL.

Serum and pituitary concentrations of prolactin and growth hormone in mice during a twenty-four hour period.

The objective of this study was to investigate changes in the secretion of prolactin (PRL) and growth hormone (GH) occurring during a 24 h period in the mouse. Adult female mice of the C57BL/St strain and male mice of the C3H/St strain, maintained on a 14 h light and 10 h dark schedule, were used. Serum and pituitary concentrations of PRL and GH were measured by radioimmunoassay in samples collected by decapitation at hourly intervals through 24 h. Serum PRL concentrations in female mice averaged higher during the daylight hours and lower at night. However, the pattern was just the opposite in males: the values were lower during the day time and higher and variable during the night. Pituitary PRL levels dropped significantly after the onset of the dark phase in mice of both sexes. Serum GH concentrations of female mice did not fluctuate significantly with the time of the day, but those of male mice displayed a distinct flux: the levels were low from 0800 h until 1500 h, began to rise in the afternoon, and remained relatively high throughout the night. Pituitary levels of GH did not change with time in mice of either sex. The data suggest the existence of daily rhythms in the secretion of PRL and GH in mice, with marked differences related to sex. In general, the changes were most pronounced for serum PRL in females and for serum GH in males.