Peripheral estrogen receptor-alpha selectively modulates the waveform of GH secretory bursts in healthy women.
Veldhuis. Johannes D JD; Keenan. Daniel M DM; Bowers. Cyril Y CY
Key Findings
- Peripheral estrogen‑receptor‑alpha (blocked by fulvestrant) controls the waveform (duration) of GH secretory bursts.
- GHRP‑2 (a ghrelin analog) lengthens GH bursts regardless of estrogen presence, but estrogen can limit the ability of other secretagogues (like l‑arginine) to do the same.
- Blocking estrogen receptors with fulvestrant extends GH bursts triggered by GHRH and GHRP‑2, indicating a selective, peripheral mechanism.
Practical Outcomes
- For biohackers using GHRP‑2 to boost GH, a woman's estrogen status may affect how long the GH surge lasts. Timing GHRP‑2 doses when estrogen levels are lower (e.g., certain phases of the menstrual cycle or with anti‑estrogenic compounds) could potentially enhance the duration of GH release. However, the findings are mechanistic and not a direct dosing protocol, so users should experiment cautiously and consider hormonal context.
Summary
The study shows that estrogen acting through peripheral estrogen‑receptor‑alpha changes the shape of growth‑hormone (GH) release bursts in women. Blocking this receptor or adding estrogen can lengthen or shorten how long a GH burst lasts, and the effect depends on which GH‑stimulating agent (like GHRP‑2) is used.
Abstract
Estradiol (E(2)) drives growth hormone (GH) secretion via estrogen receptors (ER) located in the hypothalamus and pituitary gland. ERalpha is expressed in GH releasing hormone (GHRH) neurons and GH-secreting cells (somatotropes). Moreover, estrogen regulates receptors for somatostatin, GHR peptide (GHRP, ghrelin), and GH itself, while potentiating signaling by IGF-I. Given this complex network, one cannot a priori predict the selective roles of hypothalamic compared with pituitary ER pathways. To make such a distinction, we introduce an investigative model comprising 1) specific ERalpha blockade with a pure antiestrogen, fulvestrant, that does not penetrate the blood-brain barrier; 2) graded transdermal E(2) administration, which doubles GH concentrations in postmenopausal women; 3) stimulation of fasting GH secretion by pairs of GHRH, GHRP-2 (a ghrelin analog), and l-arginine (to putatively limit somatostatin outflow); and 4) implementation of a flexible waveform deconvolution model to estimate the shape of secretory bursts independently of their size. The combined strategy unveiled that 1) E(2) prolongs GH secretory bursts via fulvestrant-antagonizable mechanisms; 2) fulvestrant extends GHRH/GHRP-2-stimulated secretory bursts; 3) l-arginine/GHRP-2 stimulation lengthens GH secretory bursts whether or not E(2) is present; 4) E(2) limits the capability of l-arginine/GHRP-2 to expand GH secretory bursts, and fulvestrant does not inhibit this effect; and 5) E(2) and/or fulvestrant do not alter the time evolution of l-arginine/GHRH-induced GH secretory bursts. The collective data indicate that peripheral ERalpha-dependent mechanisms determine the shape (waveform) of in vivo GH secretory bursts and that such mechanisms operate with secretagogue selectivity.
Study Information
pubmed
2007
2007-08-08T00:00:00.000Z
10.1152/ajpregu.00438.2007