Effects of Gonadal Steroids on the Ultrastructure of GnRH Neurons in the Rhesus Monkey: Synaptic Input and Glial Apposition*

Witkin, Joan W.; Ferin, Michel; Popilskis, Sulli; Silverman, Ann‐Judith

doi:10.1210/endo-129-2-1083

Cited by 205 publications

(164 citation statements)

References 58 publications

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“…Glial cells in the median eminence contain estrogen receptors (Langub & Watson 1992) and the degree of glial apposition to LHRH neurons is decreased by estradiol treatment in adults (Witkin et al 1991) and decreases developmentally in monkeys . Glialderived transforming growth factor alpha (TGF-), acting through the epidermal growth factor receptor (EGF-r) on astrocytes stimulates LHRH secretion (Ma et al 1997) and the expression of the mRNA for TGF- (Ma et al 1992) and the EGF-r (Ma et al 1994a) in the medial basal hypothalamus increases developmentally in rats and following menarche in monkeys (Ma et al 1994b).…”

Section: Discussionmentioning

confidence: 99%

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

Wilson

1998

Journal of Endocrinology

109

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Previous data suggest that developmental increases in peripheral concentrations of insulin-like growth factor-I (IGF-I) may be one of several neuroendocrine signals that regulate the timing of puberty. In order to test this hypothesis further, normal juvenile female rhesus monkeys (Con; n=6) were compared with age-matched animals (Igf; n=4) which received a constant subcutaneous infusion of recombinant human IGF-I (110 µg/kg/day) from 18 through 36 months of age. Menstrual bleeding was monitored and ovulation was inferred from a sustained rise in serum progesterone. In order to assess the sensitivity of luteinizing hormone-releasing hormone (LHRH) neurons to excitation, the response of serum LH to the acute administration of the glutamate receptor agonist N-methyl-, -aspartic acid (NMDA) was assessed prior to menarche, 2 months following menarche, and during the follicular phase of a female's third ovulation or 50 days after a female's first ovulation. In addition, the pituitary response of LH secretion to an LHRH agonist was assessed during the follicular phase of a female's fourth ovulation or 75 days following her first ovulation.IGF-I treatment effectively elevated serum concentrations by more than 86% of the values observed in Con animals. Although the treatment also enhanced the developmental increase in IGF binding protein-3 (IGFBP-3), IGF-I was increased proportionately more, resulting in a significantly higher molar ratio of IGF-I:IGFBP-3 in treated females throughout the course of the study. Treatment with IGF-I did not affect age at menarche but did significantly advance the age of first ovulation.Consequently, the interval between menarche and first ovulation was significantly shorter in Igf compared with Con females. Although the total number of ovulations exhibited by Igf (3·8 0·3) and Con females (3·0 0·5) in the 12 months following menarche was similar, significantly more of these were characterized by normal luteal phase progesterone secretion in Igf (100% 0) compared with Con females (64% 17). An analysis of cycles with a normal luteal phase revealed that serum estradiol during the luteal phase was significantly higher in Igf compared with Con females. Finally, IGF-treated females responded to NMDA treatment with a significantly greater increase in serum LH following menarche but not prior to menarche. In contrast, the response of serum LH to an LHRH agonist did not differ between Igf and Con females.These data suggest that the premature elevation in IGF-I levels, and consequently the ratio of IGF-I:IGFBP-3, accelerates the tempo of the final stages of puberty in rhesus monkeys. This action of IGF-I is probably the result of an increase in LHRH neuronal activity and is not due to a change in pituitary sensitivity to LHRH stimulation. In addition, ovarian sensitivity to LH stimulation during the luteal phase is also increased by IGF-I. Taken together, these data suggest that developmental increases in peripheral IGF-I secretion participate in the neuroendocrine regulation of puberty in...

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Section: Discussionmentioning

confidence: 99%

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

Wilson

1998

Journal of Endocrinology

109

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“…One study in castrated juvenile and peripubertal male rhesus monkeys did not detect any developmental difference in the density of synapses onto GnRH dendrites (Perera & Plant 1997), and reported a small decrease in synaptic density on GnRH perikarya in the mediobasal hypothalamus (Perera & Plant 1997). A study in gonad-intact female rhesus monkeys did not detect any differences in synaptic densities between pubertal and adult monkeys (Witkin et al 1991).…”

Section: Neural Inputs To Gnrh Neuronsmentioning

confidence: 98%

The neuroendocrine timing of puberty

Ebling¹

2005

Reproduction

218

109

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Puberty is the attainment of fertility, a process encompassing morphological, physiological and behavioural development. The increased hypothalamic secretion of the gonadotrophin-releasing hormone decapeptide (GnRH) is essential for the activation of the pituitary -gonadal axis at puberty. The GnRH secretory network initially develops and is temporarily active during species-specific periods of fetal/neonatal development, so puberty is the secondary reactivation of an existing system. From a neurobiological perspective, the timing of puberty is therefore a function of changes in the neural systems controlling GnRH release. The large variability between individuals in the onset and progression of puberty indicates that the timing of puberty is not simply a function of chronological age. Rather, the neurotransmitter and neuromodulatory systems that impact upon the GnRH secretory network convey information about metabolic fuels, energy stores and somatic development and, for many species, information about season and social environment. The clear links demonstrated between metabolic fuel availability and reproductive function in many animal models provides evidence that the earlier onset of pubertal development observed in girls in certain US study populations is likely to relate to the increasing prevalence of overweight and obesity in adolescents.Reproduction (2005) 129 675-683

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“…The innervation pattern of synaptic inputs to GnRH neurons also varies with reproductive state (Witkin et al, 1991;Jansen et al, 2003;Adams et al, 2006). We examined the relationship between anatomical location of GnRH neurons and degree of GABA transmission associated with the GnRH surge.…”

Section: Gaba Transmission To Gnrh Neurons Is Directly Correlated Witmentioning

confidence: 99%

Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

Christian¹,

Moenter²

2007

J. Neurosci.

122

114

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Ovulation is initiated by a surge of gonadotropin-releasing hormone (GnRH) secretion by the brain. GnRH is normally under negative feedback control by ovarian steroids. During sustained exposure to estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of this steroid switches to positive, inducing the surge. Here, we used an established ovariectomized, estradiol-treated (OVXϩE) mouse model exhibiting daily surges to investigate the neurobiological mechanisms underlying this switch. Specifically, we examined changes in GABA transmission to GnRH neurons, which can be excited by GABA A receptor activation. Spontaneous GABAergic postsynaptic currents (PSCs) were recorded in GnRH neurons from OVXϩE and OVX mice in coronal and sagittal slices. There were no diurnal changes in PSC frequency in cells from OVX mice in either slice orientation. In OVXϩE cells in both orientations, PSC frequency was low during negative feedback but increased at surge onset. During the surge peak, this increase subsided in coronal slices but persisted in sagittal slices. Comparison of PSCs before and during tetrodotoxin (TTX) treatment showed TTX decreased PSC frequency in OVXϩE cells in sagittal slices, but not coronal slices. This indicates estradiol acts on multiple GABAergic afferent populations to increase transmission through both activity-dependent and -independent mechanisms. Estradiol also increased PSC amplitude during the surge. Estradiol and the diurnal cycle thus interact to induce shifts in both GABA transmission and postsynaptic response that would produce appropriate changes in GnRH neuron firing activity and hormone release.

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Effects of Gonadal Steroids on the Ultrastructure of GnRH Neurons in the Rhesus Monkey: Synaptic Input and Glial Apposition*

Cited by 205 publications

References 58 publications

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

The neuroendocrine timing of puberty

Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

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