Hyperprolactinemia in monkeys: Induction by an estrogen-progesterone synergy

Williams, Robert F.; Barber, Donald L.; Cowan, Bryan D.; Lynch, Almorris; Marut, Edward L.; Hodgen, Gary D.

doi:10.1016/0039-128x(81)90067-2

Cited by 59 publications

(22 citation statements)

References 20 publications

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“…However, if an animal is treated with estrogen for two weeks, that is "estrogen primed", and then additionally treated with progesterone, prolactin secretion increases significantly during the progesterone supplementation (Williams et al, 1981;Williams et al, 1985). The increase in prolactin secretion can be sustained for long periods with continuous estrogen+progesterone treatment provided with Silastic capsules containing crystalline steroid hormones.…”

Section: Introductionmentioning

confidence: 99%

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques

Centeno¹,

Reddy²,

Smith³

et al. 2007

European Journal of Pharmacology

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Estrogen and progesterone act on gene and protein expression in serotonin neurons in a manner that suggests serotonin neurotransmission should increase. However, measurement of extracellular serotonin in macaques was lacking. Elevated prolactin secretion can be an indicator of increased serotonergic function and prolactin is increased by combined estrogen and progesterone treatment. We examined extracellular serotonin by microdialysis in a well-characterized macaque model of steroid-induced prolactin secretion. Monkeys were fitted with 2 guide tubes directed to the arcuate nucleus of the hypothalamus. Samples (75μl/15-min interval) were obtained via a tether-swivel device through sample lines into an adjoining room. Serotonin was measured with a modified commercial enzyme linked immunoassay (ELISA) kit. Fenfluramine infused through the probe (300 μM for 2 h; n=2 trials) or administered intravenously (2.5 mg/kg; n=2 trials) caused a marked increase in extracellular serotonin and verified the efficacy of the procedure. Three monkeys were maintained with an estrogen implant for 2 weeks. Each monkey was injected with 20 mg of progesterone s.c. in oil at 1500h; microdialysis was initiated the next morning and samples were obtained for 24 h. There was a significant increase in serotonin between 40 and 43 h after the progesterone injection (P < 0.001, ANOVA). Serotonin averaged 59±1 pg/sample from 18-30 h post-progesterone injection, and averaged 76±2 pg/sample from 30-48 h post-progesterone injection (P < 0.0001; t-test). Since the increase in serotonin is delayed by ∼40 h after progesterone-injection, we speculate that the action of progesterone may involve either nuclear progestin receptors or membrane progestin receptors.

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Section: Introductionmentioning

confidence: 99%

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques

Centeno¹,

Reddy²,

Smith³

et al. 2007

European Journal of Pharmacology

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“…In addition, we observed that the addition of P to the E treatment regimen had no significant effect on TPH mRNA expression. E alone has no significant effect on serum prolactin levels, and only when P is added to ongoing E treatment are serum prolactin levels elevated (Williams et al, 1981;Bethea et al, 1996b). Therefore, the action of P on prolactin Figure 6.…”

Section: Tph Gene Expression and Prolactinmentioning

confidence: 99%

“…Prolactin release is stimulated by progesterone (P) after estrogen (E) priming in female primates (Williams et al, 1981;Bethea et al, 1996b). This effect of P on prolactin secretion is probably mediated through a neural mechanism because lactotropes do not contain P receptors (PR) (Sprangers et al, 1989(Sprangers et al, , 1990Fox et al, 1990).…”

mentioning

confidence: 99%

Ovarian Steroid Regulation of Tryptophan Hydroxylase mRNA Expression in Rhesus Macaques

et al. 1996

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Progesterone (P) stimulates prolactin secretion through an unknown neural mechanism in estrogen (E)-primed female monkeys. Serotonin is a stimulatory neurotransmitter in prolactin regulation, and this laboratory has shown previously that E induces progestin receptors (PR) in serotonin neurons. Therefore, we questioned whether E and/or EϩP increased serotonin neural function. The expression of mRNA for tryptophan hydroxylase (TPH) was examined in ovariectomized (spayed) control, E-treated (28 d), and EϩP-treated monkeys (14 d E and 14 d EϩP) using in situ hybridization and a 249 bp TPH cRNA probe generated with RT-PCR (n ϭ 5 animals/group). Densitometric analysis of film autoradiographs revealed a ninefold increase in TPH mRNA in E-treated macaques compared to spayed animals ( p Ͻ 0.05). With supplemental P treatment, TPH mRNA signal was increased fivefold over spayed animals ( p Ͻ 0.05), but was not significantly different compared to E-treated animals. These results were verified by grain counts from photographic emulsion-coated slides. There were significantly higher single-cell levels of TPH mRNA in serotonergic neurons of the dorsal raphe in E-and EϩP-treated groups ( p Ͻ 0.05). These data indicate that E induces TPH gene expression in nonhuman primates and that the addition of P has little additive effect on TPH gene expression. Thus, the action of P on prolactin secretion is probably not mediated at the level of TPH gene transcription. However, because P increases raphe serotonin content in E-primed rodents, the possibility remains that P may have other actions on post-translational processing or enzyme activity.

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“…or of a synergistic effect of estrogen and progesterone [18]. However, the physiological role of the midcycle elevation of PRL concentrations remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Effects of Prolactin on Fertilization and Cleavage of Human Oocytes

et al. 1991

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The effects of PRL on fertilization and cleavage of human oocytes and subsequent pregnancy were studied. Forty-five patients (47 cycles) with euprolactinemic normal menstrual cycles undergoing in vitro fertilization (IVF) for the treatment of tubal infertility were selected for this study. The patients were divided into three groups dependent upon their mean serum PRL concentrations for the 3 days prior to Oocyte retrieval; hypoprolactinemic ( < 10 µg/I), euprolactinemic (10–30 µg/l) and hyperprolactinemic cycles (≧30 µg/I). Multiple follicular development was induced with hMG, and 10 patients were randomized to receive bromocriptine beginning with the previous menstrual cycle. In the hypoprolactinemic cycle group the fertilization rate was significantly lower than in the hyperprolactinemic cycle group, and the cleavage rate was significantly lower than in the other groups. The fertilization rates and the cleavage rates in the hyperprolactinemic cycle group were higher than those in the euprolactinemic cycle group; however, these differences were not statistically significant. While the pregnancy rates in the euprolactinemic cycle group were higher than in the other two groups, the numbers were too small for meaningful statistical comparison. The present study demonstrates that below normal concentrations of PRL have deleterious effects on IVF outcome. These data suggest that PRL may play a beneficial stimulatory role in Oocyte maturation and the acquisition of developmental capacity.

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Hyperprolactinemia in monkeys: Induction by an estrogen-progesterone synergy

Cited by 59 publications

References 20 publications

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques

Ovarian Steroid Regulation of Tryptophan Hydroxylase mRNA Expression in Rhesus Macaques

Effects of Prolactin on Fertilization and Cleavage of Human Oocytes

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