scholarly journals In Vivo Gonadotropin-Releasing Hormone Secretion in Female Rats during Peripubertal Development and on Proestrus*

Endocrinology ◽  
2001 ◽  
Vol 142 (7) ◽  
pp. 2929-2936 ◽  
Author(s):  
Cheryl L. Sisk ◽  
Heather N. Richardson ◽  
Patrick E. Chappell ◽  
Jon E. Levine
Keyword(s):  
Pubertal Development ◽  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Female Rat ◽  
Vaginal Opening ◽  
Pubertal Maturation ◽  
Gnrh Release ◽  
Old Rats

Abstract Pubertal development in female rats is characterized by increased LH levels and the appearance of estrogen-dependent afternoon LH mini-surges. In these studies we performed the first analysis of GnRH patterns in peripubertal rats to determine whether there are similar changes in pulsatile GnRH release. Microdialysis samples were collected at 5-min intervals throughout a 5-h afternoon period from 22 rats sampled on a single day between 30–47 days of age. Adult female rats were sampled on proestrus for comparison. In 30- to 33-day-old rats, GnRH release was infrequent (2.7 pulses/5 h; n = 3), whereas intermediate pulse frequencies were observed in 34- to 37-day-old rats (6.4 pulses/5 h; n = 9) and 38- to 42-day-old (5.0 pulses/5 h; n = 5) rats. The highest GnRH pulse frequencies were observed in 43- to 47-day-old rats (9.4 pulses/5 h; n = 5). Mean GnRH pulse amplitude did not vary significantly with age. Animals sampled before vaginal opening (VO) exhibited significantly slower GnRH pulse frequencies than those sampled after vaginal opening (1.3 pulses/5 h pre-VO vs. 7.6 pulses/5 h post-VO; P= 0.01). An afternoon increase in GnRH secretion, defined operationally as a greater than 25% increase in mean GnRH levels in the last half of the sampling period and tentatively termed a mini-surge, was observed in 0%, 33%, 40%, and 60% of 30- to 33-, 34- to 37-, 38- to 42-, and 43- to 47-day-old rats, respectively. An overall increase in GnRH pulse frequency was observed in females displaying a mini-surge (9.0 pulses/5 h with mini-surge compared with 4.7 pulses/5 h with no mini-surge). The mini-surge itself, however, was associated with a late afternoon increase in GnRH pulse amplitude and not in pulse frequency. In adult proestrous rats, peak levels during the GnRH surge were an order of magnitude greater than those reached in pubertal animals. Our findings demonstrate that pubertal maturation in the female rat is associated with an acceleration of GnRH pulse generator activity and that later stages of pubertal maturation are characterized by the appearance of afternoon increases in GnRH release that may underlie previously reported mini-surges in LH.

Changes in the characteristics of pulsatile luteinizing hormone secretion during the oestrous cycle and after ovariectomy and oestrogen treatment in female rats

1982 ◽  
Vol 94 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Takashi Higuchi ◽  
Masazumi Kawakami
Keyword(s):  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Luteinizing Hormone Secretion ◽  
Oestrogen Treatment ◽  
Serum Lh ◽  
Lh Release

Changes in the characteristics of LH secretory pulses in female rats were determined in different hormonal conditions; during the oestrous cycle and after ovariectomy and oestrogen treatment. The frequency and amplitude of the LH pulses were stable during the oestrous cycle except at oestrus when a pattern could not be discerned because of low LH concentrations. These were significantly lower than those measured during other stages of the cycle. Mean LH concentrations and LH pulse amplitudes increased with time up to 30 days after ovariectomy. The frequency of the LH pulse was unchanged 4 days after ovariectomy when mean LH levels had already increased. The frequency increased 10 days after ovariectomy and then remained stable in spite of a further increase in mean serum LH concentrations. Oestradiol-17β injected into ovariectomized rats caused a decrease in LH pulse amplitude but no change in pulse frequency. One day after treatment with oestradiol benzoate no LH pulse was detectable, probably because the amplitude was too small. A generator of pulsatile LH release is postulated and an oestrogen effect on its function is discussed.

Effects of prolonged exercise on puberty and luteinizing hormone secretion in female rats

1989 ◽  
Vol 257 (6) ◽  
pp. R1359-R1364 ◽  
Author(s):  
J. M. Manning ◽  
F. H. Bronson
Keyword(s):  
Luteinizing Hormone ◽  
Prolonged Exercise ◽  
Pubertal Development ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Female Rats ◽  
Basal Secretion ◽  
Luteinizing Hormone Secretion ◽  
Moderate Growth ◽  
Catch Up

Immature female rats were required to run for prolonged periods of time to obtain food. The amount of food they earned was adequate for full pubertal development and moderate growth under nonworking conditions, but both processes were blocked by the exercise requirement. Prolonged exercise also blocked the pulsatile release of luteinizing hormone (LH); only two LH pulses were seen in seven exercising females during a total of 24 h of monitoring at 8 wk of age. By comparison, almost 1 pulse/h was seen in postpubertal, normally growing females of this same age during metestrus. When the exercising females' running requirement was relaxed at 8 wk of age they experienced rapid catch-up growth and reproductive development. Both basal secretion and LH pulse frequency increased markedly within 48 h, and most of these females ovulated during the third dark period after relaxation. Altogether, the experimental paradigm and techniques employed here yield highly predictable results, and they should prove useful for exploring other neuroendocrine pathways through which excessive exercise antagonizes reproduction.

scholarly journals Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells

2002 ◽  
pp. 261-266 ◽  
Author(s):  
M Tezuka ◽  
M Irahara ◽  
K Ogura ◽  
M Kiyokawa ◽  
T Tamura ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Pubertal Development ◽  
Effective Concentration ◽  
Female Rats ◽  
Pituitary Cells ◽  
Female Rat ◽  
Serum Leptin ◽  
Juvenile Female ◽  
Physiological Serum ◽  
Old Rats

OBJECTIVE: Leptin is an adipocyte-derived hormone, which is the product of the obese gene and it is thought to play important roles in pubertal development and maintenance of reproductive function in the female. In a study using adult male or female rats, it was found that leptin stimulated the secretion of gonadotropin directly from the pituitary in a dose-related manner. However, there is no study in juvenile female rats before puberty. METHODS: In this study, we cultured pituitary cells from 4-, 6- and 8-week-old female Wistar rats with leptin (0-10(-7)mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10(-8) mol/l). Basal or GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and their synthesis within cells were determined by radioimmunoassay (RIA). RESULTS: Leptin induced bell-shaped dose--response curves of basal LH and FSH secretion from cultured cells of every age-group of rats studied. The most effective concentration of leptin on the basal secretion of LH and FSH from 6- and 8-week-old cultured pituitary cells was 10(-10) mol/l. This leptin concentration was consistent with circulating physiological serum leptin levels at each age. As for juvenile 4-week-old pituitary cells, the most effective concentration was 10(-11) mol/l which was lower than that of 6- and 8-week-old rats. It was consistent with the circulating serum leptin levels of 4-week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and FSH were effectively controlled by leptin at concentrations similar to the serum leptin levels of given ages. CONCLUSIONS: Leptin induced pituitary cells to synthesize and secrete both LH and FSH regardless of the presence or absence of GnRH. The concentration of leptin that induced the greatest synthesis and secretion of gonadotropins from pituitary cells changed around the pubertal period. The most effective leptin concentrations in each experiment were similar to the physiological serum leptin level at each animal age. These results indicate that leptin stimulates gonadotrophs not only in the pubertal and the mature period but also in the juvenile period before puberty. It is also conceivable that leptin may modulate the sensitivity of gonadotrophs until the appearance of GnRH stimulation, and may be the factor that brings about puberty onset.

Administration of a GnRH-antagonist to immature rats affects subsequent female and male pubertal development differently

1989 ◽  
Vol 120 (6) ◽  
pp. 778-784 ◽  
Author(s):  
H. M. van den Dungen ◽  
J. A. M. J. van Dieten ◽  
F. J. H. Tilders ◽  
G. P. van Rees ◽  
J. Schoemaker
Keyword(s):  
Gnrh Antagonist ◽  
Pubertal Development ◽  
Female Rats ◽  
Female Rat ◽  
Vaginal Opening ◽  
Gonadotropin Secretion ◽  
Adult Age ◽  
Immature Male ◽  
Male And Female Rats ◽  
Testicular Weight

Abstract. Gonadotropin secretion was inhibited in immature male and female rats by sc administration of the GnRH-antagonist ORG30276 (GnRH-A) on days 6, 9, 12 and 15. In GnRH-A-treated females this resulted in suppression of the temporarily increased plasma LH and FSH levels, which normally occur in prepubertal female rats. Ovarian weight was decreased. Although vaginal opening in GnRH-A-treated rats occurred earlier, the age of 1st estrus and the number of ova shed at first ovulation were not affected. Fertility at 4 months of age was normal. After initial suppression of gonadotropin levels, the FSH levels in GnRH-A-treated males, however, sharply increased to about twice the control levels. Plasma FSH remained elevated at least until 4 months of age. The LH levels at adult age were not affected by antagonist treatment and neither were testosterone levels. Testicular weight was decreased by GnRH-A from about 50% on day 15 to about 30% at 4 months of age. Pubertal development as measured by balano-preputial separation was delayed by about 7–10 days. At 4 months of age fertility was decreased. Thus, suppression of early gonadotropin secretion by GnRH-A treatment had dramatic effects on subsequent pubertal development in the male, but not in the female rat.

scholarly journals Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pituitary Level?

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 692-698 ◽  
Author(s):  
Kellie M. Breen ◽  
Fred J. Karsch
Keyword(s):  
Plasma Cortisol ◽  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Luteinizing Hormone Secretion ◽  
Inflammatory Stress ◽  
Gnrh Secretion ◽  
Gnrh Release ◽  
Acute Increase ◽  
Lh Secretion

Abstract Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we conducted two experiments in ovariectomized ewes to determine whether an acute increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH release into pituitary portal blood or by inhibiting pituitary responsiveness to GnRH. First, we sampled pituitary portal and peripheral blood after administration of cortisol to mimic the elevation stimulated by an immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH pulse frequency, however, was unaffected. In contrast, cortisol did not suppress either parameter of GnRH secretion. Next, we assessed the effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration, and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH release.

Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study

1989 ◽  
Vol 123 (2) ◽  
pp. 347-359 ◽  
Author(s):  
F. C. W. Wu ◽  
S. M. Borrow ◽  
K. Nicol ◽  
R. Elton ◽  
W. M. Hunter
Keyword(s):  
Pubertal Development ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Cross Sectional Study ◽  
Linear Increase ◽  
Delayed Puberty ◽  
Cross Sectional ◽  
Pubertal Maturation ◽  
Gonadotrophin Secretion ◽  
Stage 1

ABSTRACT The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16·3±2·7 (s.e.m.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1–5) and clinical progress followed for a mean duration of 22·4 ± 8·5 months during which 33 hormone profiles were obtained. Nocturnal (23.00–09.00 h) LH pulse frequency increased to a peak of 0·54±0·03/h at stage 2 which was followed by a gradual decline to 0·42 ± 0·04/h at stage 5. The appearance of LH pulses in the evening (20.00–23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0·53 ±0·08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH: FSH ratio reversed from < 1 to > 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20·42±11·57 at stage 1 to 35·96 ± 20·83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude. Journal of Endocrinology (1989) 123, 347–359

scholarly journals Pubertal Acceleration of Pulsatile Gonadotropin-Releasing Hormone Release in Male Rats as Revealed by Microdialysis

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Glenn C. Harris ◽  
Jon E. Levine
Keyword(s):  
Vas Deferens ◽  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Male Rats ◽  
Male Rat ◽  
Pubertal Maturation ◽  
Repeated Sampling ◽  
Generator Activity ◽  
Mature Spermatozoa

Abstract A microdialysis technique was used in male rats to directly assess the postulate that pubertal maturation is associated with accelerated GnRH pulsatility. Juvenile male rats, postnatal d 43 or 45 (n = 4) were stereotaxically fitted with guide cannulas directed toward the lateral median eminence, and repeated microdialysis experiments were conducted over 4–6 d. In each session, samples were collected continuously over 12 h (0900–2100 h) at 5-min intervals Results from individual peripubertal animals were pooled into two time bins for postnatal d 45–47 and 48–50, respectively, and GnRH characteristics were compared between the two epochs. The GnRH pulse frequency and mean GnRH concentration were significantly elevated at 48–50 d compared with 45–47 d. The GnRH pulsatility characteristics for 45–47 d vs. 48–50 d were as follows: pulse frequency, 0.74 ± 0.16 vs. 1.79 ± 0.19 pulses/h (P &lt; 0.05); pulse amplitude, 254.1 ± 22.3 vs. 347.2 ± 15.8 Δpg/ml (difference in value from trough to peak); and mean release, 0.55 ± 0.03 vs. 2.04 ± 0.04 pg/5 min (P &lt; 0.05). An additional two rats were dialyzed only once on postnatal d 50 to assess the effects of repeated sampling; the GnRH pulse characteristics in these animals were similar to those in rats sampled for a third or fourth time on postnatal d 48–50. To further assess the possible effects of repeated sampling on GnRH release profiles, a group of adult male rats (postnatal d 95–105; n = 3) was also dialyzed on four consecutive days. In these rats no significant alteration in GnRH pulse generator activity was observed over the four sessions. Moreover, the increase in GnRH pulse frequency observed in the peripubertal rats was found to be sustained in adult animals. To better understand the temporal relationship of GnRH pulse generator activity to reproductive maturation, groups of male rats were killed from postnatal d 45–56 along with an adult group at 95–105 d (n = 5/group) and examined for physiological signs of reproductive development. Gradual increases in serum levels of LH and testosterone and decreases in FSH and inhibin B were seen from postnatal d 45–56 to adulthood. Mature spermatozoa were found in the vas deferens by postnatal d 53. Our results demonstrate that in the late juvenile stage of male rat development, GnRH pulse generator activity is gradually accelerated over the course of consecutive days. This acceleration occurs over a period during which serum LH and testosterone are rising to adult levels, and it precedes the presence of mature spermatozoa in the vas deferens by 3 d. Our observations provide direct support for the hypothesis that an acceleration of GnRH pulsatility is the critical neural stimulus for the initiation of pubertal maturation in males. The peripheral and central cues that prompt the pubertal activation of the GnRH pulse generator remain to be characterized.

EFFECTS OF AGE AND OVARIAN FUNCTION ON THE PITUITARY–THYROID SYSTEM IN FEMALE RATS

1978 ◽  
Vol 78 (2) ◽  
pp. 225-232 ◽  
Author(s):  
H. J. CHEN ◽  
P. G. WALFISH
Keyword(s):  
Ovarian Function ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lower Percentage ◽  
Female Rat ◽  
Thyrotrophin Releasing Hormone ◽  
Young Rats ◽  
Trh Stimulation ◽  
Old Rats ◽  
Absolute Concentrations

SUMMARY The effects of ovariectomy and ovariectomy and treatment with oestradiol benzoate (OB) on the basal concentration of thyrotrophin (TSH), the total concentrations and concentrations of free tri-iodothyronine (T3) and thyroxine (T4), and the concentrations of TSH, T3 and T4 observed after treatment with thyrotrophin releasing hormone (TRH) were studied in old (16–17 months of age) constant oestrous and young (3–4 months of age) oestrous rats. The untreated old control rats had significantly (P< 0·001) lower basal total T4 concentrations and percentage and absolute concentrations of free T4 and lower percentage and absolute concentrations of free T3 than untreated young rats. The basal levels of TSH in these two groups were similar and the increases in TSH after injection of TRH were identical. Two weeks after ovariectomy, no significant additional differences in hormone concentrations between old and young rats were observed. However, release of TSH induced by TRH was increased by three- to fourfold in old rats after ovariectomy compared with nine- to tenfold in young ovariectomized rats (P<0·01). Basal T4 concentrations remained unchanged in old ovariectomized rats treated for 7 days with 2 μg OB/day compared with both intact and ovariectomized rats. However, T4 concentrations in OB-treated young rats were significantly (P<0·001) reduced. Treatment with OB significantly increased both basal and TRH-induced T3 and TSH levels in old and young rats although the young rats showed a greater response (P<0·001). Two hours after injection of TRH, serum T3 concentrations in old rats increased only after OB treatment and not after ovariectomy alone or in intact rats, whereas T3 concentrations rose in all three groups of young animals. These results indicate that (1) older female rats have lower total T4, free T4 and free T3 concentrations and a lower TSH response to TRH, (2) OB treatment in young rats suppresses serum T4 but increases serum T3 and results in a greater TSH response to TRH and (3) at least one of the mechanisms accounting for the alterations in thyroid function observed in the older female rat, in addition to possible concomitant primary thyroid gland hypofunction, is a hyporesponsiveness of pituitary thyrotrophs to both endogenous negative feedback signals from low serum thyroid hormone concentrations and exogenous TRH stimulation.

scholarly journals Comparative effects of testosterone propionate, oestradiol benzoate, ICI 182,780, tamoxifen and raloxifene on hypothalamic differentiation in the female rat

2002 ◽  
Vol 172 (3) ◽  
pp. 441-448 ◽  
Author(s):  
L Pinilla ◽  
ML Barreiro ◽  
LC Gonzalez ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Positive Feedback ◽  
Testosterone Propionate ◽  
Reproductive Function ◽  
Female Rats ◽  
Normal Brain ◽  
Female Rat ◽  
Vaginal Opening ◽  
Ici 182,780 ◽  
Oestradiol Benzoate ◽  
Normal Differentiation

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.

Induction of growth hormone (GH) mRNA by pulsatile GH-releasing hormone in rats is pattern specific

2000 ◽  
Vol 278 (5) ◽  
pp. E885-E891 ◽  
Author(s):  
Russell J. Borski ◽  
Wellington Tsai ◽  
Roberta Demott-Friberg ◽  
Ariel L. Barkan
Keyword(s):  
Growth Hormone ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Somatic Growth ◽  
Pulse Amplitude ◽  
Female Rats ◽  
Mrna Levels ◽  
Female Rat ◽  
Constant Frequency ◽  
Releasing Hormone

Growth hormone-releasing hormone (GHRH) is a main inducer of growth hormone (GH) pulses in most species studied to date. There is no information regarding the pattern of GHRH secretion as a regulator of GH gene expression. We investigated the roles of the parameters of exogenous GHRH administration (frequency, amplitude, and total amount) upon induction of pituitary GH mRNA, GH content, and somatic growth in the female rat. Continuous GHRH infusions were ineffective in altering GH mRNA levels, GH stores, or weight gain. Changing GHRH pulse amplitude between 4, 8, and 16 μg/kg at a constant frequency (Q3.0 h) was only moderately effective in augmenting GH mRNA levels, whereas the 8 μg/kg and 16 μg/kg dosages stimulated weight gain by as much as 60%. When given at a 1.5-h frequency, GHRH doubled the amount of GH mRNA, elevated pituitary GH stores, and stimulated body weight gain. In the rat model, pulsatile but not continuous GHRH administration is effective in inducing pituitary GH mRNA and GH content as well as somatic growth. These studies suggest that the greater growth rate, pituitary mRNA levels, and GH stores seen in male compared with female rats are likely mediated, in part, by the endogenous episodic GHRH secretory pattern present in males.

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