Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: evidence for a pituitary site of action

Three experiments (EXP) were conducted to determine the role of insulin-like growth factor-I (IGF-I) in the control of growth hormone (GH) and LH secretion. In EXP I, prepuberal gilts, 65 ± 6 kg body weight and 140 days of age received intracerebroventricular (ICV) injections of saline (n = 4), 25 μg (n = 4) or 75 μg (n = 4) IGF-I and jugular blood samples were collected. In EXP II, anterior pituitary cells in culture collected from 150-day-old prepuberal gilts (n = 6) were challenged with 0.1, 10 or 1000 nM [Ala15]-h growth hormone-releasing hormone-(1-29)NH2 (GHRH), or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 1000 nM GHRH. Secreted GH was measured at 4 and 24 h after treatment. In EXP III, anterior pituitary cells in culture collected from 150-day-old barrows (n = 5) were challenged with 10, 100 or 1000 nM gonadotropin-releasing hormone (GnRH) or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 100 nM GnRH. Secreted LH was measured at 4 h after treatment. In EXP I, serum GH and LH concentrations were unaffected by ICV IGF-I treatment. In EXP II, relative to control all doses of GHRH increased (P < 0.01) GH secretion. Only 1, 10, 30 nM IGF-I enhanced (P < 0.02) basal GH secretion at 4 h, whereas by 24 h all doses except for 30 nM IGF-I suppressed (P < 0.02) basal GH secretion compared to control wells. All doses of IGF-I in combination with 1000 nM GHRH increased (P < 0.04) the GH response to GHRH compared to GHRH alone at 4 h, whereas by 24 h all doses of IGF-I suppressed (P < 0.04) the GH response to GHRH. In EXP III, all doses of IGF-I increased (P < 0.01) basal LH levels while the LH response to GnRH was unaffected by IGF-I (P > 0.1). In conclusion, under these experimental conditions the results suggest that the pituitary is the putative site for IGF-I modulation of GH and LH secretion. Further examination of the role of IGF-I on GH and LH secretion is needed to understand the inhibitory and stimulatory action of IGF-I on GH and LH secretion.     

Blunted pubertal growth after leukemia: a new pattern of growth hormone insufficiency

Growth, age at menarche and spontaneous GH secretion were studied in girls after treatment for acute lymphoblastic leukemia (ALL). These girls had normal prepubertal growth but subnormal pubertal growth. Mean final height was 1 SD less than expected before puberty. The average age at menarche was significantly lower than the normal mean for Swedish girls. The mean 24-hour GH secretion was severely blunted and there was no increase during puberty. We suggest that girls treated for ALL, including CNS irradiation, have a relative GH insufficiency which becomes clinically obvious only when the girls cannot respond to the increased demands for GH in puberty.     

Exogenous estradiol reduces inhibition of luteinizing hormone by estradiol in prepubertal heifers

The hypothesis that high levels of exogenous estradiol administered to heifers during the prepubertal period would decrease subsequent negative feedback of estradiol on luteinizing hormone (LH) secretion was tested. Fourteen prepubertal heifers were ovariectomized on Day 0. Ovariectomized heifers received either no further treatment (OVX, n = 4), a single estradiol implant on Day 0 (OVXE, n = 5), or the single implant on Day 0 and two additional implants between Days 16 and 30 (OVXE+ E, n = 5). Ten ovary-intact heifers received either no treatment (INT, n = 5) or were administered the two estradiol implants between Days 16 and 30 (INT+ 5, n = 5). Comparison of LH secretion in OVXE to OVXE+E, and in INT to INT+E resulted in significant time-by-treatment interactions (p less than 0.05 for both). As pubertal age approached, mean concentration of LH (p less than 0.05) and pulse frequency (p less than 0.05) increased more rapidly in OVXE+E and INT+E than in OVXE and INT, respectively. Amplitude of LH pulses was unaffected by treatment. When data were standardized to day of puberty in INT and INT+E heifers, mean LH concentration and LH pulse frequency increased as puberty approached in both groups. These data confirm earlier reports indicating that secretion of LH increases gradually as puberty approaches in heifers. It was concluded that administration of estradiol during the prepubertal period hastened the decline in the subsequent negative feedback of estradiol. Precocious puberty was not induced in ovary-intact females.     

Estradiol regulation of luteinizing hormone secretion in heifers of two breed types that reach puberty at different ages

The working hypothesis was that 17 beta-estradiol (E(2)) negative feedback on the hypothalamic-pituitary axis in regulation of LH secretion decreases during peripuberty in heifers of 2 different genotypes. We investigated whether Bos indicus heifers had a period postpuberty, as compared with prepuberty, of greater E(2) inhibition of LH secretion at a time when heifers of this genotype have been reported to have a period of anestrus. Prepubertal heifers 9 mo of age of 2 genotypes (B. indicus and B. taurus) were assigned to 3 groups (6 animals/group) to either remain intact (control), be ovariectomized, or be ovariectomized and implanted with E(2). Variables evaluated from 10 to 28 mo of age were circulating concentrations of progesterone (P(4)), presence of corpora lutea, and pulsatile pattern of LH release. Results confirmed that B. taurus heifers attained puberty at younger ages (P < 0.001) and at lower live weights (P = 0.015) than did B. indicus heifers (507 +/- 37 days of age vs. 678 +/- 7 days of age; 259 +/- 14 kg vs. 312 +/- 11 kg; respectively). There was cessation of E(2) inhibition of LH pulses coincident with the onset of puberty in heifers of both breed types but at a much younger age in B. taurus heifers. There was no evidence of enhanced negative feedback of E(2) on LH secretion subsequent to puberty in B. indicus heifers nor was there cessation of estrous cycles in control heifers of either breed type after puberty.     

Modulation of growth hormone, luteinizing hormone, and testosterone secretion by excitatory amino acids in boars

Ketamine hydrochloride, an n-methyl-d-aspartate (NMDA) receptor antagonist was used in an experiment that tested the hypothesis that fasting-induced increases in growth hormone (GH) secretion is mediated by excitatory amino acid (EAA) neurotransmission in boars. The effects of the drug on circulating concentrations of luteinizing hormone (LH) and testosterone were also evaluated. Blood was sampled at 15-min intervals for 8 h from 12 boars fitted with jugular vein catheters. At Hours 4 and 6, fasted boars (feed was withdrawn 48 h before the start of blood sampling) received i.m. injections of ketamine (19.9 mg/kg body weight; n=4) or .9% saline (n=4). Boars allowed feed on an ad libitum basis (n=4) received i.v. injections of n-methyl-d,l-aspartate (NMA; 2.5 mg/kg body weight), an NMDA receptor agonist, at Hours 4 and 6. Secretion of GH increased after NMA injections but was unaffected by treatment with ketamine or saline. Circulating concentrations of LH and testosterone were increased by injections of ketamine but were unaffected by injections of NMA or saline. Our results suggest that NMA is a potent GH secretagogue, but do not support the hypothesis that EAA neurotransmission drives the increased GH secretion displayed in fasted boars. Our finding that ketamine increased LH and testosterone release supports the notion that EAA have inhibitory effects on gonadotropin secretion in acutely fasted swine.     

Prenatal androgens and the timing of seasonal reproductive transitions in sheep.

Both the onset of puberty in the lamb and the annual resumption of reproductive activity in adult male and female sheep are characterized by increased secretion of LH due to reduced responsiveness to steroid inhibition. However, the timing of puberty is sexually differentiated, for males undergo a reduction in sensitivity to steroid feedback at 10 wk of age, whereas females remain highly responsive to steroid inhibition until 30 wk. This sex difference is determined by androgens in utero. The present study was conducted to determine whether a sex difference exists in the timing of seasonal transitions in adult males and females. We compared serum LH in gonadectomized, estradiol-treated males (n = 7), females (n = 6), and androgenized females (n = 5) from blood samples collected twice weekly for one year. As determined by changes in the pattern of LH secretion, the onset and termination of the autumn breeding season were not different between males, females, and androgenized females (termination: 1 February +/- 4 days, mean +/- SE all groups; onset: males, 22 August +/- 4 days; females, 5 September +/- 18 days; androgenized females, 16 September +/- 10.5 days). However, there was a transient increase in LH (20 May to 23 June) in males, but not in females or androgenized females. Although no effects of prenatal testosterone were evident in the control of LH secretion in adult androgenized females, LH secretion in androgenized males was elevated throughout the nonbreeding season in 3 of 5 animals, indicating that exogenous testosterone may reduce seasonal increases in responsiveness to steroid inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone deficiency: permanence and diagnosis in young adults

OBJECTIVE: To optimize the tools for diagnosing idiopathic growth hormone (GH) deficiency. METHODS: We compared the data of 43 young adults treated for GH deficiency before and after GH treatment and puberty. Those with organic lesions were assigned to group 1 (n = 9), those with certain GH deficiency (n = 11) to group 2 and those with no criterion of certitude of GH deficiency to group 3 (n = 23). RESULTS: Group 1 patients: the GH peaks at first [1.5 +/- (SE) 0.4 microg/l] and second (1.9 +/- 0.7 microg/l) evaluations before treatment were similar to those at the third evaluation (1.2 +/- 0.8 microg/l) after treatment. Group 2 patients: they had similar peaks (2.6 +/- 0.8, 2.9 +/- 0.5 and 5.5 +/- 1.4 microg/l). Group 3 patients: the peaks increased from 4.9 +/- 0.4 and 4.8 +/- 0.4 to 18.4 +/- 2.3 microg/l (p < 0.0001); 87% had a GH peak >10 microg/l at this evaluation. The plasma insulin-like growth factor 1 was initially below -2 z-score in 12/13 of these patients and similarly low in 4/17 patients at the third evaluation. The growth rates of the three groups before and their increase during the 1st year of treatment were similar. CONCLUSION: Almost all patients with GH deficiency before puberty without criteria of certitude had a normal GH peak after puberty. Some of these patients probably had a transiently low GH secretion.     

Reduced pulsatile luteinizing hormone and testosterone secretion with aging in the male rat

To identify possible age-dependent changes in the feedback relationship between the brain-pituitary and testes, we examined the minute-to-minute patterns of plasma luteinizing hormone (LH) and testosterone (T) in intact, young male rats and compared these profiles to those of old animals. Young (3 mo; n = 11) and old (22 mo; n = 12) Sprague-Dawley rats were fitted with indwelling venous catheters and between 24 and 48 h later, were bled without anesthesia, by remote sampling, at 10-min intervals for 8 h. Blood samples of 400 microliter were withdrawn, and an equivalent volume of a blood replacement mixture was infused after each sample. Plasma LH and T levels in each sample were measured by radioimmunoassay (RIA). Plasma T levels in old animals failed to show the transient oscillations observed in young animals. Mean plasma T levels were 50% lower in old compared to young animals (P less than 0.001). Plasma patterns of LH in old animals, like their younger counterparts, showed statistically significant episodic increases, whose apparent pulse frequency was inappropriately low for their circulating T level (although not statistically different from the young group). Pulse amplitude in the old animals was 66% lower in the old compared to the young group (P less than 0.015). We conclude that age-associated alterations in brain mechanisms governing LH secretion underline these endocrine changes.     

Estradiol influences on pattern of gonadotropin secretion in bovine males during the period of changed responses to estradiol feedback in age-matched females

When ovaries are removed prior to puberty, administration of exogenous 17 beta-estradiol (E2) decreases concentrations of luteinizing hormone (LH) below that of ovariectomized heifers receiving no E2. Subsequent to the time age-matched intact heifers reach puberty, exogenous E2 increases secretion of LH in ovariectomized heifers above that of ovariectomized heifers receiving no E2. The hypothesis that E2 would inhibit gonadotropin secretion in bovine males during the time E2 no longer inhibited gonadotropin secretion in age-matched bovine females was tested. Males (n = 12) and females (n = 12) were gonadectomized at 241 +/- 3 days of age, and half of each sex (6 males and 6 females) were administered a 27-cm E2 implant. An additional group of males (n = 6) and females (n = 6) remained intact and served as controls. Blood samples were collected (to quantify LH and follicle-stimulating hormone [FSH]) from all animals at 15-min intervals for 24 h at 1, 7, 13, 17, 21, 25, 29, 33, 37, and 43 wk after gonadectomy. Additional blood samples were collected twice weekly from control females to monitor progesterone and onset of corpus luteum function (451 days of age). E2 inhibited frequency of pulses of LH (p less than 0.01) and decreased mean concentration of LH and FSH (p less than 0.01) at Week 1 in gonadectomized males treated with E2 compared to gonadectomized males not administered E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine mechanisms of puberty in heifers: estradiol negative feedback regulation of luteinizing hormone secretion

The hypothesis that luteinizing hormone (LH) secretion in prepubertal females is responsive to estradiol negative feedback and that decreased feedback occurs as puberty approaches was tested in heifers. In the first experiment, seven heifers were maintained prepubertal by dietary energy restriction until 508 days of age (Day 0). All heifers were placed on a high-energy diet on Day 0 at which time they received no additional treatment (CONT), were ovariectomized (OVX) or were ovariectomized and subcutaneously implanted with estradiol-17 beta (OVX-E2). This feeding regimen was used to synchronize reproductive state in all heifers. A second experiment was performed with 16 prepubertal heifers using the same treatments at 266 days (Day 0) of age (CONT, OVX and OVX-E2) but no dietary intake manipulation. In both experiments, LH secretion increased rapidly following ovariectomy in OVX heifers. In the initial experiment, LH secretion was maintained at a low level in OVX-E2 heifers until a synchronous rapid increase was noted coincidental with puberty in the CONT heifer. In the second experiment, LH secretion increased gradually in OVX-E2 heifers and attained castrate levels coincidental with puberty in CONT heifers. A gradual increase in LH secretion occurred as puberty approached in CONT heifers. These results indicate that: a) LH secretion in prepubertal heifers is responsive to estradiol negative feedback; and b) estradiol negative feedback decreases during the prepubertal period in beef heifers.     

Circulating concentrations of luteinizing hormone, testosterone, and growth hormone after naloxone treatment in sexually mature boars

The effects of naloxone, an antagonist of opioid peptides, on circulating concentrations of luteinizing hormone (LH), testosterone, and growth hormone (GH) were determined in sexually mature boars. Blood samples were collected at 15-min intervals for three hr from five crossbred boars. Two hr after initiation of blood sampling, boars received an i.v. challenge of naloxone (1 mg/kg body weight; n=2) or 0.9% saline (n=3). Twenty-four hr later the experiment was repeated, but boars that previously received naloxone received saline and vice versa. A time by treatment interaction (p=0.09) was detected for concentrations of LH in serum, and levels of LH were greater (p<0.03) after treatment with naloxone compared to saline. Concentrations of testosterone in serum were affected by time (p<0.01), but not treatment (p= 0.59) or treatment by time (p=0.74). A treatment by time interaction (p=0.02) was detected for serum GH concentrations. Levels of GH increased in saline-treated boars (p<0.01), but not in boars receiving naloxone (p>0.1). Our results are consistent with the theory that opioid peptides suppress LH secretion and stimulate GH release in sexually mature boars.     

Growth hormone-releasing factor (GRF) induced growth hormone advances puberty in female buffaloes

Exogenous bovine growth hormone-releasing factor (bGRF) at the dose rate of 10 microg/100 kg body weight was administered intravenously (i.v.) to six Murrah buffalo heifers as treatment group, while another six buffalo heifers served as control group which received the vehicle (0.9% NaCl solution) at an interval of 15 days for a period of 9 months to study the effect of bGRF on puberty onset associated with temporal hormonal changes in peri-pubertal buffalo heifers. Blood samples were collected at 3-day interval from all the animals during the experimental period and plasma harvested was assayed for growth hormonal (GH), luteinizing hormone (LH) and progesterone. The day that plasma progesterone was greater than 1.0 ng/ml for three consecutive sampling days was defined as the day of puberty. Exogenous bGRF administration increased (P = 0.02) plasma GH concentration in treatment group over control group during the treatment of bGRF as well as during the peri-pubertal period. Plasma progesterone concentrations increased transiently earlier (P = 0.05) by 58.5 days in bGRF-treated buffaloes than that in the control group. However, plasma LH concentrations were unaffected by the treatment of bGRF (P = 0.48). Both plasma GH and LH in the buffalo heifers increased (P < 0.01) over time preceding puberty and the higher hormonal concentrations were maintained during the onset of puberty, and thereafter, the concentrations of both the hormones declined (P < 0.05) after puberty. GH and LH were positively correlated both before puberty (r = +0.59 and +0.63; P < 0.05 for control and treatment group, respectively) and after puberty (r = +0.42 and +0.46; P < 0.05 for control and treatment group, respectively) indicating the interaction and/or close relationship of GH and LH in the mechanism of puberty in buffalo species.     

Serum luteinizing hormone, growth hormone and insulin-like growth factor-I after releasing hormone challenge in prepubertal ewe lambs selected for twinning

Two studies evaluated hormonal markers as indicators of the onset of puberty in Debouillet sheep selected for twinning. In Trial 1, 29 ewe lambs (50 +/- 0.5 kg, 159 to 187 d of age) were given 10 microg GnRH (i.v.) on September 15 and blood was collected at 30 min intervals after the injection for 2 h. Additional samples were taken twice weekly and progesterone (P4) was measured. The day that serum P4 was greater than 1 ng/mL for 2 consecutive sampling days was classified as the day of puberty. Average day of puberty was October 12 (average age at puberty was 199 d) and ewes with values less or greater than the average were classified as early or late, respectively. Average weight at GnRH challenge was 50 kg and ewes weighing less or more were classified as light or heavy, respectively. Early ewes weighed more (P = 0.01) and reached puberty sooner (P = 0.01) than late ewes. Heavy lambs reached puberty earlier, weighed more at GnRH challenge, and had more LH area under the curve (AUC, P < 0.05) than light ewes. In Trial 2, we gave 27 ewe lambs (54 +/- 0.9 kg, 173 to 189 d of age) a single i.v. injection of 10 microg GnRH and 10 microg GHRH on September 17. Average day of puberty was October 13, average weight was 54 kg, and average age at puberty was 208 d. Categories were designated as described for Trial 1. Early lambs reached puberty sooner (P = 0.01) and weighed more (P = 0.01) than late lambs, but the puberty groups had similar LH AUC (P = 0.64) and GH AUC (P = 0.75), whereas IGF-I was greater (P = 0.01) in early puberty ewes than in late puberty ewes. Heavy lambs reached puberty earlier (P = 0.06), weighed more (P = 0.01), and tended (P = 0.11) to have more GH AUC than light ewes. No difference was observed in LH AUC or IGF-I between weight groups (P > 0.15). Results suggest that serum LH after GnRH is not a reliable indicator of the onset of puberty in ewe lambs selected for twinning, but heavier ewes tended to produce more GH after a GHRH challenge and reach puberty earlier than lighter ewe lambs.     

Leptin prevents fasting-mediated reductions in pulsatile secretion of luteinizing hormone and enhances its gonadotropin-releasing hormone-mediated release in heifers

We tested the hypothesis that leptin could prevent fasting-mediated reductions in pulsatile secretion and modify GnRH-mediated release of LH in heifers approaching puberty. Thirteen crossbred, prepubertal heifers (13.5-16 mo; 280-350 kg) exhibiting frequencies of pulses of LH between 0.67 and 1 pulse/h, were assigned randomly to two groups: 1). control (n = 6), fasted for 72 h with s.c. injections of saline at 12-h intervals, and 2). leptin (n = 7), fasted for 72 h with s.c. injections of oleptin (19.2 microg/kg) at 12-h intervals. Blood samples were collected intensively for 6 h on Days 0 and 3. This was followed on Day 3 with sequential administration of physiological (0.0011 microg/kg, i.v.) and pharmacological (0.22 microg/kg, i.v.) doses of GnRH and additional blood sampling. Leptin treatment increased (P = 0.0003) plasma concentrations of leptin 5-6-fold compared to controls. Fasting caused a marked decline (P = 0.01) between Days 0 and 3 in the frequency of LH pulses in controls; however, this effect was prevented in the leptin group, with pulse frequency increasing (P < 0.008) from Day 0 to 3. Leptin treatment increased GnRH-induced release of LH at both low (P = 0.04) and high (P = 0.02) doses. Plasma insulin and insulin-like growth factor-1 were reduced by fasting and unaffected by leptin. Leptin increased mean concentrations of growth hormone. Results indicate, for the first time, that exogenous leptin can prevent fasting-mediated reductions in the frequency of LH pulses and modify GnRH-mediated release of LH in intact, prepubertal heifers.     

Secretions of GH, FSH and LH during sleep of the normal child and the child with retarded growth]

In normal children the major GH release begins during NREM sleep of first cycle. At puberty secretion of gonadotropins is enhanced and secretion of LH occurs with the same periodicity as the sleep cycles. Two groups of dwarfish are seen: the first lacks both GH secretion during sleep and the increase of gonadotropins at puberty. The second group exhibits GH, LH and FSH secretion patterns similar to normal children. Study of secretion patterns of GH, FSH and LH during sleep in children can document the degree of maturation of the hypothalamic pituitary hormonal system.     

Endocrine mechanisms of puberty in heifers. Role of hypothalamo-pituitary estradiol receptors in the negative feedback of estradiol on luteinizing hormone secretion

The hypothesis tested was that the decline in negative feedback of estradiol on secretion of luteinizing hormone (LH) that occurs as puberty approaches in heifers results from a decline in the number of receptors for estradiol in the hypothalamus and/or pituitary. In addition, associated changes in receptors for luteinizing hormone-releasing hormone (LHRH) in the pituitary, ovarian follicle development, and uterine growth were characterized. Fifty prepubertal heifers, 234 to 264 days of age, were used. Six heifers of median body weight were designated controls, and sequential blood samples were collected at 20-min intervals for 24 h every 2 wk from 249 days of age through puberty and analyzed for concentrations of LH. Frequency of LH pulses/24 h was regressed on number of days prepuberty to develop a prediction equation for puberty. Thirty of the remaining 44 heifers were killed at 253, 302, and 351 days of age (n = 10/group), and tissues for described analyses were collected. Three to 5 days before tissue collection, sequential blood samples were obtained from these heifers, as described for control heifers to determine frequency of release of LH. With this information, number of days prepuberty at the time of tissue collection was estimated from the prediction equation developed with data from control heifers. The average age at puberty in control heifers was 366 days. The average age at puberty of heifers that were not killed or included in the control group (n = 14) was 360 days. Receptor and morphological data were related to the estimated onset of puberty. Cytosolic concentration of receptors for estradiol (fmoles receptor/mg cytosolic protein) in the anterior hypothalamus, medial basal hypothalamus, and anterior pituitary declined (p less than 0.05) as puberty approached. No change in concentration of receptors for estradiol was observed in the stalk median eminence or preoptic area. The concentration of receptors for LHRH in the anterior pituitary did not change as puberty approached. Uterine weight increased rapidly during the 50 days preceding puberty. The number of small, medium, or large follicles and the wet, pressed, or dry weight of the ovaries did not change as puberty approached. Follicles with a diameter greater than 12 mm were found only in the 3 heifers estimated to be closest to puberty at the time of tissue collection. The hypothesis that the decline in estradiol feedback on secretion of LH during the prepubertal period in heifers may result from a decline in the concentration of binding sites for estradiol at the hypothalamus and/or pituitary is supported by this study.     

Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly

Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretion.     

N-methyl-d, l-aspartate stimulates growth hormone but not luteinizing hormone secretion in the sheep

The objective of this experiment was to determine the effects of N-methyl-d, l-aspartate (NMA) on luteinizing hormone (LH) and growth hormone (GH) secretion in castrated male sheep. Blood was sampled from Hampshire wethers every 15 min for 8 hr on day 1. At 4 and 6 hr after the initiation of the experiment, wethers were treated i.v. with NMA at a dose of 12 mg/kg body weight (n = 5) or .9% saline (n = 5). The dosage of NMA was within the range of doses that was previously demonstrated to stimulate LH secretion in monkeys. Blood samples were also collected every 15 min for 1 hr on day 2, beginning 24 hr after the first injection of NMA or saline. Treatment with NMA had no effect on mean LH concentrations, LH pulse frequency or LH pulse amplitude during the 4 hr period following the first injection on day 1. On day 2, however, mean LH concentrations were lower (p less than .01) in NMA versus saline-treated wethers. Conversely, administration of NMA evoked a dramatic increase (p less than .02) in mean GH concentrations on day 1. The mechanisms responsible for the effects of NMA described herein and whether or not these effects are relevant to the physiological control of LH and GH release in the sheep warrants further scrutiny.     

Estradiol increases somatomedin-C concentrations in adolescent rhesus macaques (Macaca mulatta)

Estradiol (E2) may enhance somatomedin-C (Sm-C) secretion during puberty in female rhesus monkeys. The present study evaluated the importance of age and acute changes in E2 on Sm-C secretion. Intact (INT) females at their first ovulation (age 3.5 yr; n = 6) had higher levels of Sm-C across the ovulatory cycle than did intact adults (ADT) (n = 5). Levels of Sm-C were similar for both groups during the follicular and luteal phases despite higher follicular phase levels of E2. Young, ovariectomized, E2-treated (E2OVX) females (age 3.5 yr; n = 5; E2 = 50 pg/ml) had higher basal levels of Sm-C than did either age-matched ovariectomized (OVX) females (n = 3), ovariectomized adults (OXA), or E2-treated ovariectomized adults (E2A) (E2 = 100 pg/ml). When ovariectomized groups were given E2 to induce ovulatory increases, no changes in serum Sm-C occurred. Comparisons among age-mates revealed that basal levels of Sm-C were similar between INT and E2OVX, yet these levels were higher than those for OVX. Sm-C levels were similar among all adult groups. Serum growth hormone (GH) was highest in E2OVX, next highest in INT and OVX, and lowest in all adults. Higher Sm-C levels in young animals are, thus, related to these age differences in GH concentrations and are further enhanced by basal levels of E2 and not by acute changes in this steroid. Low Sm-C secretion in adults is associated with low GH levels. Thus, the facilitory effect of basal E2 on Sm-C release is observed during conditions when basal GH levels are elevated, a situation normally limited to adolescence.     

Absence of an increase in gonad-independent drive to pulsatile luteinizing hormone secretion during photoperiod-induced puberty

This study was conducted to determine if photoperiod can influence the pattern of luteinizing hormone (LH) secretion in the absence of the ovaries in the developing female sheep. Lambs were raised in a photoperiod sequence (short, long, short days) known to induce puberty between 30 and 35 wk of age, or in a photoperiod (only short days) that prevents puberty during the first year. Their ovaries were removed at 10 wk of age, and the detailed pattern of LH was assessed (samples at 12-min intervals for 4 h) each 3- to 5-wk period between 9 and 45 wk of age. Rapid LH pulses (40- to 50-min interpulse interval) were evident within a few weeks after ovariectomy in both groups of females. Those exposed to the artificial photoperiod sequence that induces normal sexual maturity did not increase their pulse frequency further during the pubertal period. Moreover, their LH pulse frequencies were not greater than those in agonadal females exposed to the photoperiod that delays puberty. These findings indicate that photoperiodic induction of puberty in the sheep does not require steroid-independent modulation of pulsatile LH secretion.