Pituitary GH Content Research Articles

Different response to maternal hypothyroidism during the first and second half of gestation in the rat.

Female rats were mated and thyroidectomized (T) on the same day and divided into four groups. Three groups were subsequently treated daily with 1.8 micrograms L-T4/100 g body wt: 1) for the first 12 days [T + T4 (I)]; 2) from the 12th day until death [T + T4 (II)]; or 3) for the entire 21-day study [T + T4 (I + II)]. The other T animals were maintained without treatment. (T), and another group of mated rats were sham operated (C). Maternal body weight increase during gestation did not differ between T + T4 (I + II) and C dams, whereas it was smaller in T dams from the 7th gestational day onward. Neither interruption of T4 treatment in the T + T4 (I) rats after the 12th day nor treatment initiated at that time in the T + T4 (II) group modified their body weights. At day 21, the weights of the maternal conceptus-free body and liver, the placenta, and the fetuses were lower in the T and T + T4 (II) animals than in either the C and the T + T4 (I + II) animals. Maternal plasma T4 and pituitary GH content were reduced, and plasma TSH was enhanced in both T and T + T4 (I) dams. In fetuses, plasma TSH concentration was augmented in T and T + T4 (I) rats and unchanged in T + T4 (II) animals when compared with those of T + T4 (I + II). Pituitary GH content was reduced in T and T + T4 (II) fetuses and unchanged in the T + T4 (I) group. We propose that maternal thyroidectomy greatly decreases the thyroid hormone levels in embryonic structures during the first half of gestation and inhibits normal maternal metabolic changes during this period. In addition to interfering with normal fetal development, these effects reduce the quantity of maternal substrates available to fetuses during the last phase of gestation. In contrast, when maternal hypothyroidism occurs during the second half of gestation, the effects are not as detrimental because fetal thyroid gland activity is adequate, and maternal catabolic adaptations are not impaired.

Correlation of rat pituitary prolactin messenger ribonucleic acid and hormone content with serum levels during the estrogen-induced surge.

The model of the serum PRL surge generated in the ovariectomized rat after estradiol benzoate (EB) treatment was used to study the relationship between serum and pituitary PRL levels and pituitary PRL mRNA levels. Adult ovariectomized rats were injected sc with 7 micrograms EB or vehicle at noon on day 0. Three days later (day 3), the rats were decapitated every 4 h over a 24-h period (0800 h on day 3 to 0400 h on day 4) for determination of serum and pituitary PRL and GH levels by RIA. In addition, PRL and GH mRNA content was determined using dot blot hybridization with cDNAs. Administration of EB resulted in a significant rise in serum PRL levels at 1200, 1600, and 2000 h on day 3 compared to control values. At other times, serum PRL levels in the EB group were the same as control values. EB treatment also elicited a marked increase in pituitary PRL content at all time periods examined except during (1600 and 2000 h) and after the PRL surge (2400 h on day 3) when there was a significant reduction in stored pituitary PRL. The pituitary PRL mRNA content in the EB-treated group was significantly elevated (4- to 6-fold) over control levels throughout the study. Furthermore, PRL mRNA levels in EB-treated rats were significantly higher at 2000 and 2400 h on day 3 than at other time periods. In contrast to its effects on PRL, EB treatment had a slight inhibitory effect on pituitary GH content at 2000 and 2400 h on day 3 compared to control values; otherwise, this steroid had no effect on serum GH levels and pituitary GH mRNA content. Interestingly, serum GH levels and pituitary GH mRNA content in both treatment and control groups fluctuated in a pattern consistent with circadian rhythms, with peak values occurring during the lights-on hours. These data show that estrogen has a stimulatory effect on pituitary content of PRL and its corresponding mRNA in the rat 3 days after injection. These elevated PRL mRNa levels may be necessary for the occurrence of PRL surges. Furthermore, the facts that serum PRL levels were elevated only at certain times (1200-2000 h on day 3) while PRL mRNA content was increased at all times in the EB-treated rats suggest a differential regulation between PRL release and biosynthesis.

Inhibitory effect of the ovaries on neonatal androgen imprinting of growth hormone secretion in female rats.

The effect of neonatal androgen treatment on the GH secretory pattern was examined in intact and ovariectomized adult female rats. Neonatal ovariectomy or sham operation was performed at 1-2 days of age; thereafter, the animals were immediately given testosterone propionate (250 micrograms) or vehicle. Other rats, also treated neonatally with testosterone, were ovariectomized 15-22 days before blood sampling. Plasma GH was measured in blood samples obtained from indwelling intraatrial cannulae every 20 min for 8 h when the animals were 100-140 days old. Plasma GH secretory patterns were analyzed by a pulse analysis computer program (PULSAR). Neonatal testosterone treatment did not affect the GH secretory pattern of female rats with intact ovaries. In contrast, neonatal androgen treatment enhanced GH pulse height as well as mean GH concentration in neonatally ovariectomized female rats to levels comparable to those in intact male rats. Neonatal testosterone administration also significantly increased GH pulse height and mean plasma GH concentration in female rats that were ovariectomized during adulthood. However, the GH secretory pattern of ovariectomized female rats given testosterone neonatally still differed markedly from that of normal males, in that GH pulses occurred less regularly and baseline levels were higher. Pituitary GH content and concentration in neonatally ovariectomized female rats were increased to levels indistinguishable from those in male rats by neonatal testosterone treatment. No significant effect of neonatal testosterone was observed in sham-operated females. Neonatal ovariectomy decreased basal plasma GH levels, but did not affect plasma GH pulse height or pituitary GH levels. The serum estradiol concentration was markedly decreased in ovariectomized female rats, but was unchanged in sham-operated rats given neonatal testosterone, raising the possibility that serum estradiol secretion mediated the antagonistic effect of the ovaries on neonatal androgen imprinting. These results indicate that the presence of ovaries can prevent the stimulatory effect of neonatal androgen exposure on GH storage and secretion in adult female rats.

Stimulation of supranormal growth in prepubertal, adult plateaued, and hypophysectomized female rats by large doses of rat growth hormone: physiological effects and adverse consequences.

A supranormal rate of growth in intact, prepubertal, 26-day-old female rats was evoked by administration of large doses of highly purified rat GH (rGH). In response to daily doses of 1 and 5 mg/rat (13.6 mg/kg BW and 68 mg/kg BW), sc, for 20 days, body weight (BW) gain increased 51% and 73%, and skeletal growth increased 27% and 40%, respectively. Serum rGH in treated rats rose as much as 69-fold greater than that of controls. Feed efficiency, the ratio of weight gained to feed consumed, increased from 19.8% to 32.0%. This rGH treatment depleted pituitary GH content as much as 58% and caused hepatomegaly. These effects, as well as the accelerated growth rate, reverted to normal after cessation of rGH treatment. Onset of puberty in rGH-treated rats was delayed an average of 2.7 days. A similar stimulatory effect on BW gain, but not skeletal growth, as well as depletion of pituitary GH content, and hepatomegaly, was elicited by rGH treatment in adult, plateaued female rats. These effects in plateaued rats reverted to normal after cessation of GH treatment, and 50% of the body weight gain was rapidly lost. The largest dose of rGH used, 5 mg/day, was apparently toxic, resulting in a 20% higher mortality rate in treated prepubertal and plateaued female rats. Antibody formation was not the cause of the toxicity, since antibodies against rGH were undetectable at the lowest dilutions of serum tested. Serum rat insulin-like growth factor I (RIA), 3.5 U/ml in untreated intact prepubertal rats, increased to 4.7 and 5.0 U/ml, respectively, after 20 days of rGH treatment. In hypophysectomized rats, serum rat insulin-like growth factor I (RIA), undetectable in controls, was increased to 1.63 U/ml after 14 days treatment with 1 mg rGH/day. This study demonstrates that greater than normal growth can be stimulated in normal female rats by administration of large doses of homologous GH, but at the risk of serious adverse effects. Possible implications for the administration of GH to non-GH-deficient children, to promote taller stature, are clear.

Somatostatin-like immunoreactivity in duck plasma, hypothalamus and neural lobe during post-hatch growth: comparison with plasma and pituitary growth hormone concentrations.

Variations in the concentrations of plasma and pituitary GH were determined in ducks for 66 and 87 days after hatch, and compared with somatostatin-like immunoreactivity (SLI) in the plasma, hypothalamus and neural lobe. Plasma GH levels gradually decreased during growth, while pituitary GH content increased. The concentration of pituitary GH increased during the first 3 weeks of age and remained relatively constant thereafter. The decline in plasma GH concentration was paralleled by a similar fall in the level of plasma SLI. While the content of hypothalamic SLI increased during development, the SLI concentration was maximal at 14 days of age and lowest in adults. The content and concentration of SLI in the neural lobe, in contrast, increased progressively during development. Gel filtration of hypothalamic and neural lobe extracts demonstrated that both young and older birds had two main peaks of SLI, corresponding to somatostatin-14 and somatostatin-28, and a third, larger form. The elution pattern of plasma SLI was similar in young and older birds and was principally composed of a large molecular species ('big' somatostatin), although an additional small peak eluting between somatostatin-28 and somatostatin-14 was eluted from a large pool of plasma from 90-day-old ducks. These results suggest that increased plasma GH levels in young birds do not result from a hypothalamic somatostatin deficiency nor from variations in molecular forms of SLI, and that the age-related decline in plasma GH concentration is not due to a deficiency in pituitary GH content. The decline in the circulating GH level during growth is probably due to an increase in hypothalamic somatostatin release.

The effect of thyroid hormones on growth hormone gene expression in vivo in rats.

Thyroid hormones are important regulators of GH synthesis and secretion. In this study we have made a detailed examination of the time-course of the effects of hypothyroidism and tri-iodothyronine (T3) replacement in the intact rat on GH gene expression in the anterior pituitary gland. Changes in pituitary cytoplasmic GH messenger (m)RNA levels were compared with total pituitary GH content and serum GH concentration during the development of hypothyroidism and following short-term T3 replacement in vivo. Hypothyroidism was associated with a fall in pituitary GH mRNA levels. Treatment of hypothyroid animals with T3 rapidly stimulated GH mRNA levels to values above those seen in euthyroid controls. The reduction in GH mRNA levels seen during the development of hypothyroidism was accompanied by a fall in serum GH and pituitary GH content, both of which were partially restored by T3 replacement. Thus thyroid hormone replacement in hypothyroidism rapidly stimulates GH mRNA synthesis, which is followed by the gradual restoration of pituitary GH stores and serum GH concentration.

Measurement of messenger ribonucleic acid for luteinizing hormone beta-subunit, alpha-subunit, growth hormone, and prolactin after hypothalamic pituitary disconnection in ovariectomized ewes.

A transnasal, transsphenoidal surgical approach was used to perform hypothalamic pituitary disconnections (HPD) in ovariectomized (OVX) ewes to examine the role of the hypothalamus in regulating the synthesis of anterior pituitary hormones. Ewes were killed at 1-3 days (n = 6), 1 week (n = 5), or 1 month (n = 5) after HPD. Pituitary glands were removed, and hemisected for analysis of hormone or messenger RNA (mRNA) content. Blot hybridization using specific complementary DNA probes was used to quantify the concentration of mRNA for LH beta-subunit, alpha-subunit, GH, and PRL. Concentrations of mRNA for LH beta- and alpha-subunits were lower (P less than 0.01) at 1-3 days after HPD than in OVX ewes. At 1 week and 1 month after HPD, concentrations of mRNA for LH beta- and alpha-subunits were near the lower limit of detection of this assay system. In contrast, for 30 days after HPD, pituitary concentrations of mRNA for GH and PRL were not different (P greater than 0.05) from those in OVX ewes. At 1 week and 1 month after HPD, pituitary content of LH, FSH, and GH was lower (P less than 0.01) than in OXV ewes. Pituitary PRL content in all HPD ewes was lower (P less than 0.05) than in OVX ewes. In a separate group of five ewes that were bled daily for 30 days after HPD, serum concentrations of LH and FSH fell dramatically during the first 3 days after HPD. In contrast, serum concentrations of GH and PRL remained similar to pre-HPD concentrations for 30 days after HPD. Thus, hypothalamic stimulation is essential for maintaining the concentration of mRNA for LH beta- and alpha-subunits within the anterior pituitary gland. Without continued hypothalamic support, pituitary and serum concentrations of LH and FSH rapidly decline. In contrast, concentrations of mRNA for GH and PRL are maintained in the absence of hypothalamic input.

Stimulation of pig growth performance by porcine growth hormone and growth hormone-releasing factor.

The current study was undertaken to determine the effects of human growth hormone-releasing factor [hpGRF-(1-44)-NH2] on growth performance in pigs and whether this response was comparable to exogenous porcine growth hormone (pGH) treatment. Preliminary studies were conducted to determine if GRF increased plasma GH concentration after iv and im injection and the nature of the dose response. Growth hormone-releasing factor stimulated the release of pGH in a dose-dependent fashion, although the individual responses varied widely among pigs. The results from the im study were used to determine the dose of GRF to use for a 30-d growth trial. Thirty-six Yorkshire-Duroc barrows (initial wt 50 kg) were randomly allotted to one of three experimental groups (C = control, GRF and pGH). Pigs were treated daily with 30 micrograms of GRF/kg body weight by im injection in the neck. Pigs treated with pGH were also given 30 micrograms/kg body weight by im injection. Growth rate was increased 10% by pGH vs C pigs (P less than .05). Growth rate was not affected by GRF; however, hot and chilled carcass weights were increased 5% vs C pigs (P less than .05). On an absolute basis, adipose tissue mass was unaffected by pGH or GRF. Carcass lipid (percent of soft-tissue mass) was decreased 13% by GRF (P less than .05) and 18% by pGH (P less than .05). Muscle mass was significantly increased by pGH but not by GRF. There was a trend for feed efficiency to be improved by GRF; however, this was not different from control pigs. In contrast, pGH increased feed efficiency 19% vs control pigs (P less than .05). Chronic administration of GRF increased anterior pituitary weight but did not affect pituitary GH content or concentration. When blood was taken 3 h post-injection, both GRF- and pGH-treated pigs had lower blood-urea nitrogen concentrations. Serum glucose was significantly elevated by both GRF and pGH treatment. This was associated with an elevation in serum insulin. These results indicate that increasing the GH concentration in blood by either exogenous GH or GRF enhances growth performance. The effects of pGH were more marked than for GRF. Further studies are needed to determine the optimal dose of GRF to administer in growth trials and the appropriate pattern of GRF administration in order to determine whether GRF will enhance pig growth performance to the extent that exogenous pGH does.

Growth hormone secretion in genetic large (LL) and small (SS) rats.

We investigated whether genetic selection for growth influences pituitary GH secretion in two strains of rats, LL (large) and SS (small). Animals were bled every 15 min for 6 h via an indwelling atrial Silastic catheter, and GH levels were determined by RIA. LL and SS males displayed a low frequency, high amplitude episodic pattern of GH secretion, with surges of GH occurring at 3- to 4-h intervals, separated by trough periods of approximately 60-120 min. In contrast, LL females showed a high frequency, low amplitude pattern of GH secretion, with GH pulses occurring every 1-2 h. The number of GH pulses in SS females was lower than that in LL females. SS males and SS females displayed lower peak amplitudes and lower baseline levels and, therefore, lower mean plasma GH levels compared to LL animals. The anterior pituitary GH content was not significantly different in LL and SS animals of either sex. Thus, the reduction of GH levels in SS animals is most likely the result of reduced release of GH-releasing factor from the hypothalamus or an attenuated pituitary sensitivity to GH-releasing factor.

Influence of endogenous growth hormone-releasing factor (GRF) on the secretion of GH during the perinatal period in the rat

Passive immunization of pregnant rats with a specific antiserum to rat GRF (GRF-AS) is followed by a decrease in fetal serum GH on the 19th day of gestation. A significant reduction in serum GH is still observed in older fetuses and newborn rats. Pituitary GH content increases in 19- and 20-day-old fetuses after GRF-AS administration to their mothers. These results suggest that endogenous fetal hypothalamic GRF (or placenta GRF) play a physiological role in the secretion of pituitary GH as early as the 19th day of fetal life and may be responsible for the peak of GH release that occurs in fetuses at the end of gestation.

Effects of a fragment of human growth hormone-releasing factor in normal and 'Little' mice.

The 'Little' mouse is characterized by a body growth rate 60% of normal due to a defect in the synthesis and storage of GH in the anterior pituitary gland. We have now investigated the effects of GH releasing factor (GRF) in these mice and in normal animals. The pituitary GH content in Little mice was only 4% of that in normal C57: +/+ mice, and was not affected by twice daily i.p. injections of human (h) GRF1-29NH2 (0.2-2 micrograms) for 14 days. This treatment also had no effect on body growth. In anaesthetized normal mice, single i.v. injections of 0.1 or 2 micrograms hGRF1-29NH2 released large amounts of GH into the plasma, whereas this peptide was ineffective in Little mice, whether or not they had been pretreated with GRF. Therefore, although pituitaries of Little mice contain significant amounts of GH, this pool is not releasable by GRF. This suggests that the dwarfism in Little mice may be partly due to a pituitary defect in GRF receptors or their stimulus-secretion coupling, rather than a deficiency in hypothalamic GRF.

Transient neonatal hyperthyroidism results in hypothyroidism in the adult rat.

Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 microgram/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P less than 0.001), and serum T4 (P less than 0.005), T3 (P less than 0.001), and TSH (P less than 0.001) concentrations. The percent decreases were 12% for T4, 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic alpha-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P less than 0.005), 52% (P less than 0.025), and 39% (P less than 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5'-deiodinase activity of adult NH rats [200 +/- (SE) 23 fmol T3/min X mg protein] was significantly decreased to 56% of control levels (355 +/- 31 fmol T3/min . mg protein; P less than 0.005). Mean pituitary T4 5'-deiodinase activity of adult NH rats (32.8 +/- 3.3 fmol T3/min . mg protein) was significantly increased compared with that of control rats (21.2 +/- 1.7 fmol T3/min . mg protein; P less than 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5'-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats.

Effect of long-term corticosteroid administration on rat pituitary growth hormone and prolactin.

In vitro corticosteroids stimulate GH synthesis by pituitary cells, while in vivo they suppress stimulated plasma GH levels. In this study we investigated in rats the effect of hydrocortisone administration for 2-4 weeks on pituitary GH content. Hydrocortisone added to the drinking water (100 mg/l) resulted in a marked stimulation of pituitary GH content after 3 and 4 weeks of treatment. No significant stimulation, however, was observed on basal GH release by the pituitary gland incubated in vitro. Further, we found that both Prl content and release were inhibited by hydrocortisone administration.

Human pancreatic growth hormone (GH)-releasing hormone stimulates GH synthesis and release in infant rats. An in vivo study.

Administration of human pancreatic GH-releasing factor 1-40 (hpGRF-40) at doses of 1, 10, 20, 100, and 500 ng/100 g BW sc induced in 10-day-old rats a clear-cut rise in plasma GH 15-min post-injection, although the effect was not dose-related and peak GH levels were already present after the lowest GRF dose. In 25-day-old rats, hpGRF induced only a slight rise in plasma GH at the dose of 500 ng/100 g BW sc, whereas it was completely ineffective at the lower doses. In 5-day-old rats, hpGRF (20 ng/100 g BW sc twice daily), administered for 5 days, induced a marked rise in pituitary GH content and plasma GH levels determined 14 h after the last hpGRF injection. In these rats, at the end of treatment, a challenge hpGRF dose (20 ng/100 g BW) induced a rise in plasma GH significantly higher than in infant rats receiving only the challenge hpGRF dose. These data show that: 1) pituitary responsiveness to hpGRF is strikingly higher in infant than in post-weaning rats; 2) in infant rats, subacute administration of hpGRF stimulates GH synthesis and release.

Rapid changes in growth hormone regulation and hypothalamic somatostatin after transection of anterolateral pathways to the medial-basal hypothalamus in the rat.

Plasma and pituitary GH content, in-vitro GH release and somatostatin-like immunoreactivity (SLI) in the stalk-median eminence were studied up to 7 days after making an anterolateral cut (ALC) around the medial-basal hypothalamus. Plasma GH concentration increased within 15 min to a very high level, then fell to a high level which was unchanged for several hours. The GH concentration then steadily decreased between days 2 and 7. The SLI content in the stalk-median eminence decreased to 3.5% of the control value within 3 days. The GH content of the anterior pituitary gland was 58.8% of the control value by 1 week after the operation but the in-vitro sensitivity to somatostatin of the GH cells failed to change. Pentobarbitone injection stimulated GH release in the sham-operated controls but decreased it in the rats with an ALC. These findings suggest that transection of somatostatin-containing fibres is followed by a rapid rise and a lasting high concentration of plasma GH which slowly returns towards lower levels in parallel with a marked depletion of pituitary GH content. In rats with transected somatostatin innervation of the median eminence, sodium pentobarbitone probably decreases GH secretion by depressing the secretion of GH-releasing hormone.

Stimulation of swine growth by porcine growth hormone.

Highly purified porcine growth hormone (pGH; USDA-B1) was administered by im injection (22 micrograms X kg body weight-1 X d-1) to rapidly growing Yorkshire barrows for 30 d. Growth hormone significantly increased growth rate (10%), feed efficiency (4%), cartilage growth and muscle mass. However, pGH did not affect carcass adipose tissue mass. Intramuscular lipid content of the longissimus was increased 50% by pGH administration. Plasma pGH concentration was elevated (7- to 11-fold) for 3 to 5 h post-injection. Chronic administration of pGH depressed pituitary GH content and concentration approximately 45%. No GH antibodies were detected in the plasma of GH-treated swine. Plasma somatomedin-C concentration was increased 55% by GH treatment 3 h post-injection. Plasma glucose and insulin concentrations were both significantly increased in GH-treated swine, suggesting that the animals had developed a state of insulin resistance. Plasma-free fatty acid concentration tended to be higher in GH-treated animals. Treatment of swine with pGH significantly decreased plasma blood urea nitrogen. Assessment of animal health during the trial and postmortem indicated that pGH administration did not have any adverse effects. In summary, treatment of young, rapidly growing swine with pGH stimulated growth performance without affecting animal health or inducing the production of GH antibodies.

Diurnal variations of plasma growth hormone, thyrotropin, thyroxine, and triiodothyronine in streptozotocin-diabetic and food-restricted rats.

The pattern of spontaneous GH, TSH, T4, and T3 secretion has been studied in male rats in response to a 15-day period of streptozotocin diabetes or food restriction. Beginning at 0900 h, groups of control (C), food-restricted (FR), diabetic (D), and insulin-treated D rats were killed every 60-90 min for a 8-h period. Food restriction resulted in a significant depression of the GH, TSH, T4, and T3 peaks, whereas diabetes caused complete suppression of episodic secretion of each hormone. Insulin (6 U/100 g BW X day for 12 days) administration to D rats restored the normal pattern of secretion. In D and FR rats, pituitary GH concentrations were lower than in C rats, whereas pituitary TSH concentrations were similar to those in controls. Thus, as compared to C rats, FR and D rats showed an inhibition in GH, TSH, T4, and T3 secretion, most marked in D animals. Since diabetes is associated with a deficiency of circulating thyroid hormones, the potential roles of T4 and T3 on pituitary GH concentration and secretion in D rats were evaluated. Treatment of D rats with insulin (3 U/100 g BW X day), T4 (1.8 micrograms/100 g BW X day), or T3 (0.30 microgram/100 g BW X day) for 12 days resulted in a significant but limited increase in pituitary GH content. When administered together with insulin, the net effects of T4 or T3 with insulin appeared additive. T4 administration to D rats produced a significant though limited increase in plasma GH concentrations and weight gain, whereas both values were unaffected by T3. Simultaneous administration of T4 and insulin resulted in significant increased plasma GH concentration to levels greater than those in C rats. However, plasma GH levels in rats treated with T3 plus insulin were greater than those in D rats, but lower than in C animals. The results indicate that the decreased pituitary GH content of D rats can be corrected, at least in part, by T4 and T3.

The effect of exteroceptive pup stimuli on the responsiveness of prolactin release mechanisms to suckling stimuli in the lactating rat.

In the lactating rat, the neural stimulus of suckling not only acutely releases PRL but also maintains the responsiveness of PRL regulatory mechanisms to subsequent nursing stimuli. Beginning near midlactation exteroceptive pup stimuli (ECS) can acutely release PRL. We have examined the capacity of this signal also to maintain the responsiveness of PRL release mechanisms to subsequent suckling stimuli. On day 14 postpartum lactating rats were either isolated from their young or exposed to ECS (without suckling) for approximately 24 h. When both groups were later nursed, plasma PRL of mothers earlier exposed to ECS rose significantly higher than that of subjects previously isolated from their young. Suckling produced a significant depletion in pituitary PRL and GH concentrations of ECS-exposed mothers; it did not produce a similar depletion in the pituitaries of the previously isolated group. When the pups were returned for suckling, ECS-exposed mothers began to nurse their pups substantially faster than did females of the isolated group. During the 6 h after nursing, the mammary glands of ECS-exposed mothers secreted milk at twice the rate of mammary glands of the isolated females. We conclude that ECS can maintain the capacity of neuroendocrine mechanisms to respond to galactopoetic hormone-releasing stimuli (consequently enhancing milk secretion) and support the maternal behavior pattern necessary for suckling to occur. As a result, ECS may become an important factor during later stages of lactation, compensating for the decline in suckling stimuli known to occur at that time.

Pituitary growth hormone response in rats during a 24-hour infusion of growth hormone-releasing factor.

The pituitary GH response during a 24-h iv infusion of GH-releasing factor (hpGRF-44; 15 micrograms/h) and to a subsequent bolus injection of hpGRF-44 (2 micrograms) was studied in conscious, freely moving male rats pretreated with antiserum against somatostatin. Within 2 h of the initiation of the hpGRF-44 infusion, plasma GH concentrations rose from 169 +/- 16 to 2465 +/- 307 (+/- SE) ng/ml. By 6 h, plasma GH concentrations began to fall. They decreased slowly and reached a nadir of 490 +/- 107 ng/ml by 12 h. Rats infused for 24 h with hpGRF-44 failed to respond to a 2-micrograms bolus injection (iv) of hpGRF-44, whereas rats infused for 24 h with saline responded with a normal increase in plasma GH. The pituitary GH content of rats treated with saline was significantly greater than that of rats treated with hpGRF-44. These results demonstrate that the capacity of the pituitary to respond to GRF can be exhausted after the chronic administration of hpGRF-44 and that this lack of response appears to be due, in part, to a depletion of pituitary stores of GH.

Hormone levels of anterior pituitary gland and serum in Nagase analbuminemia rats.

The hormone levels in the anterior pituitary gland and serum in Nagase analbuminemia rats (NAR), a mutant strain established from Sprague-Dawley rats with hyperlipidemia, were examined. For the anterior pituitary gland, the prolactin, TSH, GH, LH and FSH contents in male NAR were significantly lower than those of normal rats. In female NAR, prolactin, TSH and LH levels were also lower than those in normal rats, whereas FSH and GH were normal. For the serum, the concentrations of TSH, total T3, total and free T4, estradiol-17 beta and testosterone were examined. The serum testosterone concentration in NAR was lower than that of normal rats. Histochemical examination of the hydroxysteroid dehydrogenase (HSD) activity of testes was made in relation to the serum testosterone level. NAR testes, which are rather small compared with those of normal rats, have lower HSD activity. A higher level of serum TSH was seen in NAR. Total and free T4 concentrations were low in the male NAR only. Estradiol-17 beta and T3 concentrations in NAR were unchanged. Changes in serum LH and FSH levels during the estrous cycle in NAR were also studied. Their patterns of change are normal.