Abstract
The known interactions between the somatotropic and hypothalamic‐pituitary‐gonadal (HPG) axes have not been well delineated in older individuals. Aging‐associated decline in insulin like growth factor‐1 (IGF‐1) levels has been proposed to play a role in reproductive senescence in animals. However, the effects of GH on LH secretion are unknown in older individuals. Our objective was to determine whether GH modulates LH secretion or levels of sex steroids (SS) in healthy older (ages 65–88 years) men (n = 24) and women (n = 24) with low‐normal plasma IGF‐1 levels. In a double‐masked, placebo‐controlled (n = 24), randomized study, we evaluated the effects of GH (n = 24, 20 μg/kg sc 3×/week) for 26 weeks on nocturnal LH secretory dynamics [(8 pm to 8 am, Q20) min sampling and analyzed by multiparameter deconvolution algorithm]. Indices of LH secretion [frequency, mass per burst, pulsatile production rate, and approximate entropy (ApEn)] and fasting serum IGF‐1, SHBG, and SS (TT, fT, or E2) were measured. At baseline, all indices of LH secretion (frequency, mass per burst, pulsatile production rate) were inversely (P < 0.05) related to IGF‐1, but not to mean nocturnal serum GH concentrations. GH administration for 26 weeks increased serum IGF‐1, but exerted no significant effects on LH secretory dynamics, or concentrations of SSs (TT, fT, or E2) or SHBG in older women or men. These data suggest that GH‐mediated increases in IGF‐1 do not modulate the HPG axis in older individuals.
Highlights
The hypothalamus, pituitary gland, and gonads with feedback loops constitute the hypothalamic-pituitary-gonadal (HPG) axis (Veldhuis 2008)
The follicular phase is characterized by high-frequency luteinizing hormone (LH) pulses due to the positive feedback from increasing E2 concentrations released by the preovulatory follicles (Hall 2015) and the luteal phase is characterized by the low-frequency LH pulses
We examined the effects of exogenous growth hormone (GH) administration and its associated increase in serum insulin like growth factor-1 (IGF-1) levels on pulsatile secretion of LH in healthy older men and women with low-normal circulating levels of IGF-1 and sex steroid (SS)
Summary
The hypothalamus, pituitary gland, and gonads with feedback loops constitute the hypothalamic-pituitary-gonadal (HPG) axis (Veldhuis 2008). Effects of GH on LH Secretion hormone (FSH) from the pituitary gonadotrophs. Circulating LH and FSH act on the gonads to release sex steroid (SS) hormones which negatively feedback onto the pituitary and hypothalamus to inhibit GnRH and LH secretion. SSs such as estradiol (E2) and progesterone (P) or peptide hormones such as inhibin negatively regulate the secretion of GnRH and LH (by SSs), and FSH (by inhibin and E2) (Hall 2015). The follicular phase is characterized by high-frequency LH pulses due to the positive feedback from increasing E2 concentrations released by the preovulatory follicles (Hall 2015) and the luteal phase is characterized by the low-frequency LH pulses
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