The amplitude of nocturnal melatonin concentrations is not decreased by oestradiol and does not alter reproductive function in adolescent or adult female rhesus monkeys

1993 ◽  
Vol 137 (2) ◽  
pp. 299-309 ◽  
Author(s):  
M. E. Wilson ◽  
S. Lackey ◽  
K. Chikazawa ◽  
T. P. Gordon
Keyword(s):  
Replacement Therapy ◽  
Rhesus Monkeys ◽  
Pubertal Development ◽  
Developmental Changes ◽  
Ovulatory Cycle ◽  
Serum Samples ◽  
Night Time ◽  
Serum Progesterone ◽  
Female Rhesus ◽  
Igf I

ABSTRACT Nocturnal concentrations of melatonin in serum decline significantly with advancing pubertal development in both children and non-human primates and elevated levels may be associated with anovulation in adults. Three studies, using female rhesus monkeys, were performed to determine whether (1) the decline in nocturnal melatonin concentrations in adolescents was due to maturational increases in serum oestradiol, (2) the experimental elevation in nocturnal melatonin would delay the normal progression of puberty in post-menarchial monkeys, and (3) the experimental elevation in nocturnal melatonin would disrupt normal ovulatory function in adults. In experiment 1, juvenile female rhesus monkeys, housed indoors in a fixed photoperiod (12 h light: 12 h darkness), were assigned randomly to one of two treatment groups: ovariectomized with no replacement therapy (control; n= 4) or ovariectomized with oestradiol replacement therapy maintaining oestradiol at ∼ 90 pmol/l (treated; n= 8). Twenty-four hour as well as daytime serum samples were collected from 19 to 35 months of age. Nocturnal melatonin concentrations declined significantly in all females with advancing chronological age and this change was unaffected by oestradiol treatment. The decline in nocturnal melatonin concentrations occurred, on average, 2·0 ±0·2 months after the initial rise in serum LH in control females and 6·0 ±0·8 months in treated females. Furthermore, this decline in night-time melatonin was not related to significant developmental changes in body weight. In experiment 2, control (n = 6) and melatonintreated (treated; n =6) adolescent female monkeys were studied from −30 to +105 days from menarche. Beginning at 45 days following menarche, treated females received 30 days of nocturnal melatonin infusion to elevate levels to prepubertal values. Developmental changes in perineal swelling and coloration as well as serum oestradiol and insulin-like growth factor-I (IGF-I) were compared with values observed during the 45-day pretreatment and 30-day post-treatment conditions as well as with those observed in control females. Despite a significant elevation in nightly melatonin levels for the 30-day period in treated females, developmental changes in oestradiol, IGF-I, and perineal coloration and swelling were not different compared with the control females. In experiment 3, adult females were given melatonin nightly beginning on the first day of menses following an ovulatory cycle and treatment was continued for 45 days or until the next menstruation occurred. Melatonin was elevated to supraphysiological levels every night throughout the treatment period. Despite this elevation, an ovulation, inferred from serum progesterone levels, occurred in every female and serum oestradiol, LH or progesterone were not affected compared with the values obtained during the untreated cycle. These data indicate that the decline in nocturnal melatonin concentrations is not related to a developmental increase in oestradiol secretion. Furthermore, experimentally elevated concentrations of nocturnal melatonin did not delay the normal progression of puberty following menarche nor did it disrupt ovulatory function in adults. These data suggest that the enhanced nocturnal melatonin concentrations are not causally linked to either puberty onset or anovulatory conditions in adults. Journal of Endocrinology (1993) 137, 299–309

scholarly journals Neurobiological Mechanisms of the Onset of Puberty in Primates*

2001 ◽  
Vol 22 (1) ◽  
pp. 111-151 ◽  
Author(s):  
Ei Terasawa ◽  
David L. Fernandez
Keyword(s):  
Rhesus Monkeys ◽  
Neonatal Period ◽  
Developmental Changes ◽  
Neurosecretory System ◽  
Neuronal System ◽  
Inhibitory Neurotransmitter ◽  
Gaba Inhibition ◽  
Female Rhesus ◽  
Lhrh Release ◽  
Low Levels

Abstract An increase in pulsatile release of LHRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in LHRH release is still unclear. In primates the LHRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state in the juvenile/prepubertal period. Neither gonadal steroid hormones nor the absence of facilitatory neuronal inputs to LHRH neurons is responsible for the low levels of LHRH release before the onset of puberty in primates. Recent studies suggest that during the prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of the hypothalamus this prepubertal inhibition is removed, allowing the adult pattern of pulsatile LHRH release. In fact,γ -aminobutyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before the onset of puberty in female rhesus monkeys. In addition, it appears that the reduction in tonic GABA inhibition allows an increase in the release of glutamate as well as other neurotransmitters, which contributes to the increase in pubertal LHRH release. In this review, developmental changes in several neurotransmitter systems controlling pulsatile LHRH release are extensively reviewed.

Constant low-dose oestradiol replacement accelerates skeletal maturation and growth in ovariectomized adolescent rhesus monkeys

1993 ◽  
Vol 137 (3) ◽  
pp. 519-527 ◽  
Author(s):  
M. E. Wilson ◽  
T. P. Gordon ◽  
J. M. Tanner
Keyword(s):  
Rhesus Monkeys ◽  
Low Dose ◽  
Skeletal Maturity ◽  
Skeletal Maturation ◽  
Serum Concentrations ◽  
Treatment Control ◽  
Female Rhesus ◽  
Igf I ◽  
Growth Promoting ◽  
Tibia Length

ABSTRACT The effects of oestradiol (OE2) on adolescent growth in female rhesus monkeys were evaluated by testing the hypothesis that, upon removal of the ovary, the increase in growth normally seen at the time of puberty would be abolished and that treatment with OE2 would restore it. Juvenile monkeys (n= 12) were ovariectomized and were given either an OE2-bearing silicone elastomer capsule implanted subcutaneously to simulate mid-pubertal concentrations ('treated = ', n = 8) or no steroid treatment ('control = ', n = 4). Females were studied from 18 to 42 months of age which, in intact females, typically encompasses the prepubertal period to the occurrence of first ovulation. Over the whole period, growth in body weight, crown–rump (CR) length and tibia length for control females were less than the 95% confidence limits of females treated with OE2. However, significant spurts of growth in both CR and tibia length occurred in the control as well as treated animals, although the peak velocities were somewhat lower for non-OE2-treated animals. Peak growth velocities occurred at an earlier chronological age in treated females, although at the same degree of skeletal maturity as found in control females. Skeletal maturity was significantly advanced in treated females from 27 months onward. Serum concentrations of nocturnal GH increased significantly with advancing age in both groups, with greater increases observed in treated females. Serum concentrations of IGF-I were higher in treated females until some 30 months of age, at which point concentrations increased in a similar fashion in both groups. IGF-I concentrations were elevated in the months preceding and following the peak CR growth velocity in treated females whereas concentrations of IGF-I rose coincidently with peak CR growth in control females. These data indicate that, in the absence of OE2, growth in female monkeys has periods of acceleration and that OE2 may enhance this pre-set pattern. Furthermore, the growth-promoting effects of OE2 are determined by the degree of skeletal maturity. Once a certain degree of skeletal maturity is attained, bones may be primed for maximal growth, but, as skeletal maturity continues to advance, the effect of OE2 on growth diminishes. Journal of Endocrinology (1993) 137, 519–527

scholarly journals Developmental Changes in GnRH Release in Response to Kisspeptin Agonist and Antagonist in Female Rhesus Monkeys (Macaca mulatta): Implication for the Mechanism of Puberty

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 825-836 ◽  
Author(s):  
Kathryn A. Guerriero ◽  
Kim L. Keen ◽  
Robert P. Millar ◽  
Ei Terasawa
Keyword(s):  
Rhesus Monkeys ◽  
Developmental Stages ◽  
Developmental Changes ◽  
Partial Recovery ◽  
Ovarian Steroid ◽  
Medial Basal Hypothalamus ◽  
Female Rhesus ◽  
Gnrh Release ◽  
Agonist And Antagonist

Kisspeptin (KP) and KP-1 receptor (KISS1R) have emerged as important upstream regulators in the control of puberty. However, how developmental changes in KP-KISS1R contribute to the pubertal increase in GnRH release still remains elusive. In this study, we examined the effects of the KP agonist, human KP-10 (hKP-10), and the KP antagonist, peptide 234, on in vivo GnRH release in prepubertal and pubertal ovarian-intact female rhesus monkeys using a microdialysis method. We found that direct infusion of hKP-10 into the medial basal hypothalamus and stalk-median eminence region stimulated GnRH release in a dose-responsive manner, whereas infusion of peptide 234 suppressed GnRH release in both developmental stages. Because ovarian steroid feedback on GnRH release becomes prominent after the initiation of puberty in primates, we further examined whether ovarian steroids modify the GnRH response to hKP-10. Results demonstrate that the hKP-10-induced stimulation of GnRH release was eliminated by ovariectomy in pubertal, but not prepubertal, monkeys. Furthermore, replacement of estradiol into ovariectomized pubertal monkeys resulted in a partial recovery of the hKP-10-induced GnRH release. Collectively, these results suggest that a KISS1R-mediated mechanism, in addition to the pubertal increase in KP-54 release we previously reported, contributes to the pubertal increase in GnRH release and that there is a switch from an ovarian steroid-independent to -dependent mechanism in the response of GnRH to KP.

IGF-I administration advances the decrease in hypersensitivity to oestradiol negative feedback inhibition of serum LH in adolescent female rhesus monkeys

1995 ◽  
Vol 145 (1) ◽  
pp. 121-130 ◽  
Author(s):  
M E Wilson
Keyword(s):  
Negative Feedback ◽  
Rhesus Monkeys ◽  
Feedback Inhibition ◽  
Control Group ◽  
Feedback Effects ◽  
Adult Females ◽  
Serum Lh ◽  
Female Rhesus ◽  
Igf I ◽  
Intermediate Dose

Abstract Developmental increases in serum LH were assessed in female rhesus monkeys to test the hypotheses that (1) the final stages of puberty are characterized by a decrease in hypersensitivity to oestradiol negative feedback of LH and (2) that increases in IGF-I secretion accelerate this decrease in hypersensitivity. In order to test the first hypothesis, serum LH in the absence of oestradiol and in response to three doses of oestradiol were compared between ovariectomized adult (n=6) and adolescent female monkeys (control group; n=6). The control females were not treated with oestradiol until serum LH had risen to within the 95% confidence interval of serum LH observed in ovariectomized adults. Doses of oestradiol achieved serum levels of approximately 80 ('low'), 160 ('intermediate'), and 250 ('high') pmol/l. For control group females, treatment with the next higher dose of oestradiol was not initiated until serum LH was no longer suppressed by the lower dose. Treatment with oestradiol produced a dose-dependent suppression in serum LH in adults. In contrast, low-dose oestradiol maximally suppressed serum LH throughout the initial treatment period in the control group compared with the adult females. The low oestradiol dose effectively suppressed serum LH throughout the study period in 4/6 of the control group and became ineffective at suppressing LH after 8 months of treatment in 2/6 control group females. Initiation of the intermediate dose of oestradiol to these females again maximally suppressed LH compared with adult females. In order to determine whether IGF-I regulates this change in hypersensitivity to oestradiol negative feedback, a second group of ovariectomized, adolescent monkeys (n=6) were treated chronically with IGF-I to elevate serum IGF-I levels above those of control group females. Using the same protocol described for the control females, developmental changes in serum LH in the absence of oestradiol and in response to oestradiol negative feedback were evaluated. Treatment with IGF-I had no effect on the initial increases in serum LH occurring in the absence of oestradiol. In contrast, the decrease in hypersensitivity to the negative feedback effects of the low oestradiol dose was significantly accelerated in IGF-I-treated females, as the interval from the initiation of treatment to the point at which serum LH was no longer suppressed was shorter in IGF-I-treated (4·4±0·7 months; mean ± s.e.m.) compared with control group females (8·4±1·9 months). Although none of the control group females escaped from the negative feedback effects of the intermediate dose of oestradiol during the course of the study, 2/7 of the IGF-I-treated females did so within 5·5±1·4 months of the initiation of the treatment. The present data indicate that the later stages of puberty in female monkeys are characterized by a decreasing in sensitivity to oestradiol negative feedback inhibition of serum LH and that timing this decrease is regulated by circulating concentrations of IGF-I. These data confirm earlier reports that the developmental increases in the GH axis accelerate the tempo of puberty without affecting its onset. Journal of Endocrinology (1995) 145, 121–130

Anterior hypothalamic lesions and pubertal development in female rhesus monkeys

1983 ◽  
Vol 7 (3) ◽  
pp. 321-330 ◽  
Author(s):  
J VANDERWERFFTENBOSCH ◽  
D DIERSCHKE ◽  
E TERASAWA ◽  
A SLOB
Keyword(s):  
Rhesus Monkeys ◽  
Pubertal Development ◽  
Hypothalamic Lesions ◽  
Female Rhesus

Administration of IGF-I affects the GH axis and adolescent growth in normal monkeys

1997 ◽  
Vol 153 (2) ◽  
pp. 327-335 ◽  
Author(s):  
M E Wilson
Keyword(s):  
Rhesus Monkeys ◽  
Binding Protein ◽  
Pituitary Function ◽  
Serum Concentrations ◽  
Estradiol Treatment ◽  
Juvenile Female ◽  
Female Rhesus ◽  
Igf I ◽  
Serum Gh ◽  
Igfbp 3

Abstract The present study examined the effects of IGF-I on serum concentrations of IGF binding protein-3 (IGFBP-3) and GH and assessed how treatment with estradiol and IGF-I would stimulate adolescent growth in monkeys with normal pituitary function. In study I, ovariectomized, juvenile female rhesus monkeys (21 months of age; n=6) received a bolus injection of IGF-I (1 mg/kg s.c.) and serum samples were collected periodically through 48 h. The consequential elevation in serum IGF-I resulted in a parallel increase in serum IGFBP-3 at 1 and 3 h after treatment with values returning to baseline by 7 h. In contrast, the elevation in serum IGF-I resulted in a significant decline in serum GH within 3 h of treatment. These data confirm that an elevation in IGF-I increases IGFBP-3 while simultaneously acting in a negative feedback capacity to inhibit GH. In study II, ovariectomized, juvenile female rhesus monkeys served either as controls (Con, n=6) or received a constant s.c. infusion of IGF-I (300 μg/day; Igf, n=6) from 13 through 32 months of age. At approximately 26 months, females entered an estradiol-treatment protocol in which they received alternating blocks of 3 weeks of estradiol followed by 3 weeks of no estradiol. As found in study I, the elevation in serum IGF-I resulted in a significant increase in serum IGFBP-3 throughout the study in Igf compared with Con females. Estradiol administration significantly increased serum IGF-I and IGFBP-3 levels in both groups. Although the nano-molar ratio of IGF-I to IGFBP-3 was consistently higher in Igf females, the magnitude of the change in IGF-I:IGFBP-3 following estradiol treatment was similar between groups. Finally, the age-dependent increase in serum GH was dampened in Igf compared with Con females and the increase in response to estradiol was less in Igf females. Although total growth in crown-rump length was similar in both groups, Igf females grew more prior to estradiol replacement while Con females grew more once estradiol treatment was initiated. In addition, skeletal maturity was advanced more quickly in Igf females once estradiol treatment had been initiated. These data suggest that, in female monkeys with normal pituitary function, IGF-I administration inhibits endogenous GH secretion but is capable of stimulating crownrump growth. Although IGF-I increased serum levels of IGFBP-3, the increase was not proportional to the increase in serum IGF-I achieved by the treatment. These data would suggest that IGF-I may regulate the release of this binding protein but that GH may be required to maintain equi-molar proportions of IGF-I to IGFBP-3. In addition, the observation that serum concentrations of IGF-I were increased further in IGF-I-treated females by the administration of estradiol without a change in serum GH, suggests that estradiol has a direct effect on IGF-I synthesis and release independent of GH. Journal of Endocrinology (1997) 153, 327–335

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