Aging attenuates the pituitary response to gonadotropin-releasing hormone.
BACKGROUND
Complex changes in GnRH secretion occur with aging in women, but little is known about the effect of aging on the pituitary per se.


OBJECTIVE
The aim of the study was to determine whether pituitary responsiveness to GnRH is attenuated with aging.


METHODS
A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness in Clinical Research Center studies at an academic medical center.


METHODS
Subjects were healthy postmenopausal women (PMW) aged 48-57 yr (n = 10) or 70-77 yr (n= 9).


METHODS
A suppressive dose of the NAL-GLU GnRH antagonist (150 microg/kg sc) was administered and was followed by GnRH doses of 25, 75, 250, or 750 ng/kg iv every 4 h.


RESULTS
The LH response to GnRH was attenuated with aging (P = 0.05) with an interaction between age and dose (P = 0.01) such that the LH amplitude was less in older PMW at the higher doses (250 ng/kg, 50 +/- 9 vs. 29 +/- 4.9 IU/liter, for young and old PMW, respectively, P = 0.02; and 750 ng/kg, 97.7 +/- 11 vs. 70.2 +/- 9.3 IU/liter, P = 0.002), but not the lower doses of GnRH. The FSH response to GnRH was also attenuated with aging in PMW (P = 0.005).


CONCLUSIONS
In studies that isolated the pituitary from endogenous GnRH stimulation, aging attenuated the LH and FSH responses to exogenous GnRH in PMW. These studies indicate that the pituitary plays a role in the decline in gonadotropin levels with aging, further supporting the potential contribution of age-associated changes in both hypothalamic and pituitary function to reproductive senescence.
Shaw
Natalie D
ND
Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Srouji
Serene S
SS
Histed
Stephanie N
SN
McCurnin
Kristin E
KE
Hall
Janet E
JE
D000368:Aged; D000375:Aging / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D017698:Postmenopause
D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone