RPEP-00032 · 1985Normal thymosin alpha 1 levels were similar across all groups of women tested, regardless of their hormonal status. This peptide appears unaffected by estrogen.
Thymosin beta 4 told a different story. Castrated women not receiving estrogen had reduced levels. Postmenopausal women on chronic estrogen therapy had even lower thymosin beta 4. Castrated women on estrogen also showed decreased levels.
Normal women in the early follicular phase (low estrogen point of the menstrual cycle), women with premature ovarian failure, and postmenopausal women not on estrogen all had similar thymosin beta 4 levels. But the premature ovarian failure and postmenopausal groups showed wide variation, suggesting these are not uniform populations.
Suh, B Y; Naylor, P H; Goldstein, A L; Rebar, R W · Cross Sectional
RPEP-00083 · 1988Alpha-helical CRF9-41 (a CRF receptor blocker) applied to hypothalamic slices in vitro caused beta-endorphin and met-enkephalin to drop significantly within 10 minutes. At the same time, LHRH (luteinizing hormone-releasing hormone) rose significantly.
Dynorphin also decreased but the change was not statistically significant.
When the antagonist was removed, the pattern reversed within 10 minutes: beta-endorphin, met-enkephalin, and dynorphin rose back up while LHRH fell back down.
The same results were obtained in vivo using push-pull perfusion of the arcuate-median eminence region in anesthetized rats. This confirmed the in vitro findings in living animals.
Nikolarakis, K E; Almeida, O F; Sirinathsinghji, D J; Herz, A · Animal Study
RPEP-00084 · 1988GABA at concentrations from 10^-8 to 10^-4 M caused a dose-dependent increase in GnRH release from rat hypothalamic slices. The GABA-A receptor agonist isoguvacine replicated this, while the GABA-B agonist baclofen had no effect. The GABA-A antagonist SR95103 blocked the GABA effect.
Blockade of nerve conduction with tetrodotoxin abolished GABA's stimulatory effect, meaning it works through neural circuits, not directly on GnRH cells.
Naloxone (opioid blocker) prevented GABA-induced GnRH release. The CRF antagonist also blocked it. CRF itself decreased GnRH release, and GABA could not reverse this.
GABA stimulated the release of beta-endorphin, dynorphin, and met-enkephalin from the same tissue, connecting opioid peptide release to the control of reproduction.
Nikolarakis, K E; Loeffler, J P; Almeida, O F; Herz, A · In Vitro
RPEP-00093 · 1988Three opioid peptide families showed distinct, non-overlapping distributions in the preoptic brain region.
Beta-endorphin fibers were mainly in the periventricular nucleus. Dynorphin B fibers were more uniformly distributed with few cell bodies. Enkephalin (peptide E) had hundreds of cell bodies, concentrated in specific nuclei.
The key sexual dimorphism: male rats had significantly more enkephalin cells in the anteroventral periventricular nucleus (AVPv) than females. This was despite the AVPv being physically larger in female rats.
This sex difference was at least partially dependent on perinatal gonadal steroids. Early hormone exposure during the critical developmental window permanently organized the number of enkephalin cells, a process called organizational hormone effects.
No sex difference was found in enkephalin cells in the anterodorsal preoptic nucleus, showing the dimorphism was region-specific, not a general property of enkephalin neurons.
Simerly, R B; McCall, L D; Watson, S J · Animal Study
RPEP-00211 · 1991Pregnancy and DES treatment altered pituitary met-enkephalin and dynorphin content in patterns paralleling oxytocin and vasopressin changes.
Schriefer, J A · Animal Study
RPEP-00220 · 1992Human placenta contains exclusively kappa opioid receptors (MW ~63,000). They regulate acetylcholine and hCG/placental lactogen release. Receptor numbers correlate with birth weight at term.
Ahmed, M S; Cemerikic, B; Agbas, A · Review
RPEP-00226 · 1992Order of potency for hCG release: kappa >>> mu > delta. All three produced bell-shaped dose-response curves. Kappa dominance confirmed.
Cemerikic, B; Schabbing, R; Ahmed, M S · In Vitro
RPEP-00229 · 1992Beta-endorphin (10^-6 M) reduced uterine contractions, prostaglandin synthesis, and calcium uptake. Naloxone did not block it. Other opioids were inactive.
Faletti, A; Bassi, D; Gimeno, A L; Gimeno, M A · Animal Study
RPEP-00243 · 1992DMEPA (enkephalin analog) inhibited estradiol-induced uterine DNA synthesis by ~50% when given 1-2 hours before measurement. Naloxone partially reversed the effect.
Ordög, T; Vértes, Z; Vértes, M · Animal Study
RPEP-00255 · 1992Thymosin beta 4 peaked early and declined with age. hCG challenge depressed thymosin beta 4. Testosterone modulated both thymosin beta 4 and alpha 1 levels. Castration altered the patterns.
Wise, T H · Animal Study
RPEP-00256 · 1993CRF fibers terminate within the hypothalamus and directly modulate the release of growth hormone, gonadotropins, and opioid peptides through local synaptic connections.
Almeida, O F; Hassan, A H; Holsboer, F · Review
RPEP-00261 · 1993Naloxone significantly increased plasma oxytocin on days 15, 18, and 21 of pregnancy but not in non-pregnant, early pregnant, or post-partum rats.
Douglas, A J; Dye, S; Leng, G; Russell, J A; Bicknell, R J · Animal Study
RPEP-00284 · 1993Big dynorphin (prodynorphin 209-240) caused a 5.1-fold increase in serum prolactin in turkeys, mediated through kappa opioid receptors.
Youngren, O M; Silsby, J L; Phillips, R E; el Halawani, M E · Animal Study
RPEP-00322 · 1995Specific opioid receptors were found in pig granulosa cells and corpora lutea, with receptor numbers increasing during follicular maturation.
Hamada, H; Kishioka, S; Yamoto, M; Nakano, R · In Vitro
RPEP-00327 · 1995All tested opioid peptides inhibited arcuate neuron firing, with beta-endorphin affecting 55% of neurons, consistent across different hormonal states.
Lin, J Y; Pan, J T · In Vitro
RPEP-00412 · 1997Anti-beta-endorphin antibodies blocked suckling-induced prolactin release without affecting tuberoinfundibular dopaminergic neurons, proving beta-endorphin is an essential mediator.
Jaworski, R P; Callahan, P; Janik, J · Animal Study
RPEP-00493 · 1998GHRP receptor mRNA was detected in human fetal pituitary by RT-PCR, and GHRP-2 stimulated dose-dependent GH release from cultured fetal pituitary cells, demonstrating functional GH secretagogue receptors are present before birth.
Shimon, I; Yan, X; Melmed, S · In Vitro
RPEP-00617 · 2000Oral estradiol supplementation in postmenopausal women modulated continuous GHRP-2-driven GH secretion, increasing IGF-1 response but altering GH pulse dynamics, revealing estrogen-GH secretagogue interactions important for clinical dosing.
Shah, N; Evans, W S; Bowers, C Y; Veldhuis, J D · RCT
RPEP-00643 · 2001Estradiol replacement selectively relieved GH autonegative feedback on GHRP-2-stimulated (not GHRH-stimulated) GH secretion in postmenopausal women, demonstrating pathway-specific estrogen modulation of the somatotropic axis.
Anderson, S M; Wideman, L; Patrie, J T; Weltman, A; Bowers, C Y; Veldhuis, J D · RCT
RPEP-00704 · 2001Estrogen is the proximate sex steroid sustaining GH secretion across the human lifespan, modulating GHRP sensitivity, somatostatin withdrawal, and GH feedback through specific neuroendocrine mechanisms that decline with menopause.
Veldhuis, J D; Evans, W S; Bowers, C Y; Anderson, S · Review
RPEP-00782 · 2002Oral E2 selectively enhanced the GHRP-2 hypothalamic signaling component during combined GHRP-2/GHRH stimulation while reducing somatostatin restraint in postmenopausal women, revealing pathway-specific estrogen modulation of dual-peptide GH stimulation.
Veldhuis, J D; Evans, W S; Bowers, C Y · Clinical Trial
RPEP-00832 · 2003Mu-opioid receptor agonists inhibited basal and LH-stimulated progesterone and androstenedione production in porcine theca cells in a dose-dependent manner, demonstrating direct opioid peptide control of ovarian steroidogenesis.
Kaminski, T; Siawrys, G; Bogacka, I; Okrasa, S; Przala, J · In Vitro
RPEP-00840 · 2003Opioid peptides directly inhibited uterine cell proliferation in a developmental stage-dependent manner: strongest in immature tissue, diminishing with maturation, with different receptor subtypes active at different stages.
Környei, J L; Vértes, Z; Kovács, K A; Göcze, P M; Vértes, M · In Vitro
RPEP-00916 · 2004Ghrelin's integrated control of appetite, adiposity, and GnRH/gonadotropin secretion links eating disorders, obesity, and reproductive dysfunction through a common hormonal mechanism.
Gottero, C; Broglio, F; Prodam, F; Destefanis, S; Bellone, S; Benso, A; Gauna, C; Arvat, E; van der Lely, A J; Ghigo, E · Review
RPEP-00932 · 2004Opioid peptides differentially modulated granulosa cell steroidogenesis: inhibiting progesterone while stimulating estradiol through kappa and mu receptor subtypes, revealing a complex opioid regulatory layer in ovarian hormone production.
Kaminski, T; Siawrys, C; Bogacka, I; Okrasa, S; Przala, J · In Vitro
RPEP-01269 · 2007Weight loss in overweight women modified gut hormone profiles: increased postprandial ghrelin (hunger) and reduced PYY satiety responses — hormonal changes that favor weight regain, explaining the biological basis of yo-yo dieting and weight loss plateau.
Moran, Lisa J; Noakes, Manny; Clifton, Peter M; Wittert, Gary A; Le Roux, Carel W; Ghatei, Mohammed A; Bloom, Stephen R; Norman, Robert J · Clinical Trial
RPEP-01300 · 2007Peripheral ER-alpha activation selectively altered GH secretory burst waveform (mass, amplitude, duration) without changing overall GH output in women — demonstrating estrogen modulates the QUALITY of GH release, not just quantity, with functional implications for GH bioactivity.
Veldhuis, Johannes D; Keenan, Daniel M; Bowers, Cyril Y · Clinical Trial
RPEP-01325 · 2008Kisspeptins activate GPR54 receptor to control GnRH neuron firing, serving as the essential gatekeeper for puberty onset and adult fertility — GPR54 mutations cause both absent puberty (hypogonadotropic hypogonadism) and infertility, establishing kisspeptin as the master reproductive switch.
Colledge, W H · Review
RPEP-01406 · 2008Ghrelin modulated steroidogenesis (progesterone, estradiol) and cell proliferation in prepubertal porcine ovarian follicles, establishing a direct ovarian ghrelin system with implications for reproductive development and fertility.
Rak, A; Gregoraszczuk, E L · In Vitro
RPEP-05027 · 2020Tachykinins (NKB, NKA, substance P) initiate puberty by stimulating kisspeptin neuron activation in the hypothalamus, with loss of tachykinin signaling causing delayed/absent puberty in humans and mice.
Navarro, Víctor M · Review
RPEP-05077 · 2020Defb20 is exclusively expressed in the caput epididymis, down-regulated by gonadectomy and efferent duct ligation, and first expressed at postnatal day 20, indicating androgen-dependent regulation linked to sperm maturation.
Pujianto, Dwi Ari; Muliawati, Dewi; Rizki, Meidika Dara; Parisudha, Annisa; Hardiyanto, Lutfi · Animal Study
RPEP-05318 · 2021Substance P at 5 nmol/kg restored spermatogenesis in busulfan-treated azoospermic mice by stimulating spermatogonia proliferation via NK1R-ERK1/2 signaling.
Chen, Zhihong; Liu, Minjie; Hu, Jin-Hua; Gao, Yong; Deng, Chunhua; Jiang, Mei Hua · Animal
RPEP-05370 · 2021Maternal TB4 treatment (6 mg/kg on days E14 and E17) increased newborn cranio-caudal length and accelerated development of lungs, heart, kidneys, cerebral cortex, and notochord compared to control newborns.
Faa, G; Piras, M; Mancuso, L; Coni, P; Pichiri, G; Orrù, G; Fanni, D; Gerosa, C; Cao, G; Taibi, R; Pavone, P; Castagnola, M · Animal
RPEP-09118 · 2024Neurokinin B at three doses (1 μg, 1 ng, and 10 pg) administered intraperitoneally for 12 days increased seminal vesicle weight, epithelial height, and seminal fructose levels in a dose-dependent manner. Senktide (an NK3R agonist) produced similar effects. SB222200 (an NK3R antagonist) slightly decreased these parameters.
Light microscopy showed increased epithelial height and folding in all neurokinin B and senktide groups. Immunohistochemistry for NK3 receptor expression showed no change with treatment, suggesting the receptor is constitutively expressed.
Critically, all effects reversed when rats were kept for 12 days without treatment, indicating the changes are stimulatory and reversible rather than permanent.
Ramzan, Muhammad Haris; Shah, Mohsin; Ramzan, Faiqah · Animal Study
RPEP-12929 · 2025GIP significantly reduced testosterone secretion in PCOS mouse models and NCI-H295R cells, suppressing androgen biosynthesis through specific molecular pathways identified via RNA sequencing.
Pan, Mengru; Qian, Yifan; Jiang, Linlin; Cao, Chunwei; Li, Lin · Animal Study