Relation Between Levels of Circulating Ovarian Steroids and Pituitary Gonadotropin Content During the Menstrual Cycle of the Rhesus Monkey1

Hotchkiss, J.; Dierschke, Donald J.; Butler, Walter; Fritz, G. R.; Knobil, E.

doi:10.1095/biolreprod26.2.241

Cited by 24 publications

(26 citation statements)

References 25 publications

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“…The concentration of P in the serum of P and E+P-treated groups was 6.17±0.65 ng/ml and 3.89±0.73 ng/ml, respectively. The concentrations of E and P are similar to that observed in the mid-luteal phase (Hotchkiss et al, 1982). The concentrations of E and P in the serum of the Ovx group were 8.0±2 pg/ml and 0.09±0.03 ng/ml, respectively (significantly different from steroid-treated monkeys by ANOVAs, ps = 0.0001).…”

Section: Resultssupporting

confidence: 81%

Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe

Rivera

Bethea

2012

Neuroscience

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Dendritic spines are the basic structural units of neuronal plasticity. Intracellular signaling cascades that promote spinogenesis have centered on RhoGTPases. We found that ovarian steroids increase gene expression of RhoGTPases (RhoA, Cdc42 and Rac) in laser-captured serotonin neurons. We sought to confirm that the increases observed in gene expression translate to the protein level. In addition, a preliminary study was conducted to determine whether an increase in spines occurs via detection of the spine marker protein, PSD-95. Adult ovariectomized (Ovx) monkeys were treated with estradiol (E), progesterone (P) or E+P for 1 month. Sections through the dorsal raphe nucleus were immunostained for RhoA and Cdc42 (n = 3-4/group). The number and positive pixel area of RhoA-positive cells, and the positive pixel area of Cdc42-positive fibers were determined. Upon combining E and E+P treated groups, there was a significant increase in the average and total cell number and positive pixel area of RhoA-positive cells. E, P and E+P treatments individually or combined, also increased the average and total positive pixel area of Cdc42-positive fibers. With remaining sections from 2 animals in each group, we conducted a preliminary examination of the regulation of PSD-95 protein expression. PSD-95, a postsynaptic scaffold protein, was examined with immunogold silver staining (n = 2/group) and the total number of PSD-95-positive puncta was determined with stereology across 4 levels of the dorsal raphe. E, P and E+P treatment significantly increased the total number of PSD-95-positive puncta. Together, these findings indicate that ovarian steroids act to increase gene and protein expression of two pivotal RhoGTPases involved in spinogenesis and preliminarily indicate that an increased number of spines and/or synapses result from this action. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and in turn, increase serotonin neuronal activity throughout the brain.

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Section: Resultssupporting

confidence: 81%

Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe

Rivera

Bethea

2012

Neuroscience

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“…These unexpected findings are discussed in the light implantation of E2-containing Silastic capsules in a manner designed to establish levels of E2 in blood that would fall within the normal range as observed during the follicular phase of the menstrual cycle (13). E2 infusion (three animals) was at the rate of 65.5 or 100 ng of E2 per kg per hr in normal saline containing 2-20%o ethanol and 0.1% gelatin for 8-10 hr (14).…”

Section: Bstractmentioning

confidence: 91%

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

Kesner

Wilson

Kaufman

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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BSTRACTIn the rhesus monkey (Macaca mulatta), the of current models of the neuroendocrine control of the f quency of pulsatile gonadotropic hormone release is relaprimate menstrual cycle. tiHely constant in the face of widely varying levels of estradiol ( 2) in the peripheral circulation-e.g., in the course of the f Ilicular phase of the menstrual cycle and after ovariectomy. MATERIALS he frequency of luteinizing hormone (LH) pulses during the f llicular phase of the menstrual cycle in women (1-6) and rhesus monkeys (7,8) does not appear to differ from that o served in the total absence of ovarian estrogen secretion ( 2, 9). Furthermore, the rising tide of estrogen during the f llicular phase of the cycle is not accompanied by a reduct on in LH pulse frequency. On the contrary, it has been s ggested that the time of the initiation of the preovulatory g nadotropin surge may be associated with a small increase i the frequency of LH secretory episodes (3-6, 8). These servations dictate the conclusion that estrogens have little cr no effect on the modulation of LH pulse frequency, in ontrast to progesterone, which unambiguously decelerates t ie pulsatile release of this gonadotropic hormone (1-6, 8, 10, 1).The present report describes the profound inhibition of ypothalamic gonadotropin-releasing hormone (GnRH) ulse generator activity and the consequent reduction in LH ulse frequency or total arrest of pulsatile LH secretion in I ng-term ovariectomized rhesus monkeys exposed to physi logical levels of exogenous estradiol (E2) as well as in sponse to supraphysiological doses of E2, which initiate LH rges. These unexpected findings are discussed in the light 1 e publication costs of this article were defrayed in part by page charge Pament. This article must therefore be hereby marked "advertisement" accordance with 18 U.S.C. §1734 solely to indicate this fact. 8745implantation of E2-containing Silastic capsules in a manner designed to establish levels of E2 in blood that would fall within the normal range as observed during the follicular phase of the menstrual cycle (13). E2 infusion (three animals) was at the rate of 65.5 or 100 ng of E2 per kg per hr in normal saline containing 2-20%o ethanol and 0.1% gelatin for 8-10 hr (14). MUA recording and blood sampling were begun 4.5-6 hr prior to the initiation of the infusions and were continued throughout the treatment period. Thus, each animal in this and the subsequent studies served as its own control. Silastic capsules containing crystalline E2 (15) were implanted into eight monkeys. Eight-hour recording sessions were conducted before and for 1-4 weeks after capsule implantation.LH surges were induced in two chair-restrained animals by the administration s.c. of 83 pug of E2 benzoate per kg Abbreviations: LH, luteinizing hormone; GnRH, gonadotropinreleasing hormone; E2, estradiol; MUA, multiple unit activity.

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“…Female cynomolgus monkeys (Macaca fascicularis) were used as the alternative model to study reproductive hormones and function because the monkeys have physiological systems including hormonal pattern, ovarian cycle, and reproductive function that are similar to those of humans (32,33). Moreover, to study the effects of P. mirifica containing phytoestrogens on changes of serum levels of hormones in humans is very difficult due to uncontrolled diet and follow-up factors.…”

Section: Introductionmentioning

confidence: 99%

Estrogenic Effects of Pueraria mirifica on the Menstrual Cycle and Hormone-Related Ovarian Functions in Cyclic Female Cynomolgus Monkeys

et al. 2004

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Abstract. This study investigated the estrogenic effect of Pueraria mirifica (P. mirifica) on menstrual cycle length and hormone-related ovarian function. Nine normal cyclic monkeys (Macaca fascicularis) were separated into 3 groups; each group was force fed with a single dose of 10, 100, and 1,000 mg of P. mirifica. The experimental schedule was separated into the pre-treatment and post-treatment periods. Blood samples were collected on days 3, 9 -14, 19, 24, 29, and every 10 days until the next menstruation for one and two menstrual cycles during two consecutive periods and assayed for serum levels of gonadotropins and ovarian hormones. The result showed a significant increase in lengths of the follicular phase and total menstrual cycle in monkeys treated with 1,000 mg of P. mirifica, but no change in menstrual cycle length in monkeys treated with 10 and 100 mg of P. mirifica. Serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, or immunoreactive-inhibin did not change during the first and second menstrual cycles of the post-treatment period for all monkey groups. Our findings demonstrate that although changes in hormonal levels could not be observed in this study, a single dose of 1,000 mg of P. mirifica can disturb ovarian function and menstrual cycle in monkeys.

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Relation Between Levels of Circulating Ovarian Steroids and Pituitary Gonadotropin Content During the Menstrual Cycle of the Rhesus Monkey1

Cited by 24 publications

References 25 publications

Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe

Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

Estrogenic Effects of Pueraria mirifica on the Menstrual Cycle and Hormone-Related Ovarian Functions in Cyclic Female Cynomolgus Monkeys

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