Sex‐linked differences in cortisol, ACTH and prolactin responses to 5‐hydroxy‐tryptophan in healthy controls and minor and major depressed patients

Abstract

Some researchers have found that the administration of 5-hydroxytryptophan (5-HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender-related differences in cortisol responses to 5-HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5-HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 mg L-5-HTP (orally, non-enteric coated). We found that healthy men had significantly higher cortisol responses to L-5-HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L-5-HTP. The amplitudes of the cortisol, ACTH and PRL responses to L-5-HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.

Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness

“…Conversely, the fall in ACTH efficacy with age in men is consistent with declining cortisol levels inferred in other investigations (2,16,24,40,43,49,55,61,63,64,78). Our finding of opposing effects of age on ACTH-cortisol efficacy in men and women explain the absence of an overall effect of age when data from both sexes are considered together.…”

“…For example, in one study in eight hypogonadal men, cortisol production rates were normal (77), whereas in another study, leuprolideinduced gonadoprivation unmasked greater ACTH and cortisol responses to corticotropin-releasing hormones (CRH) in young and middle-aged men than premenopausal women (59). Analyses of young hypogonadal adults further suggest that serotoninergic agonists and psychosocial stress stimulate greater corticotropic-adrenal responses in young men than young women (49,61). On the other hand, cortisol concentrations are reportedly higher in women than men during early sleep, dexamethasone suppression, interleukin-6 infusion, growth hormone-releasing hormone (GHRH) injection, CRH stimulation, physostigmine administration, and psychosocial stress (8,43,48,64,78).…”

Central Serotonergic Effects of m-Chlorophenylpiperazine (mCPP) among Normal Control Adolescents

“…Further, it is noteworthy that similar neuroendocrine responsivity noted among healthy adolescents and healthy adults may not generalize to depressed patients. For instance, as part of an ongoing larger study, we have earlier reported (Ghaziuddin et al, 2000) augmented PRL and cortisol responses to mCPP among depressed adolescents, which was in contrast to reduced PRL responsivity found in the majority of studies involving depressed adults (Maes et al, 1989;Cowen and Charig, 1987;Lopez-Ibor et al, 1989). It is possible that dissimilar neuroendocrine responses among depressed adolescents and adults, despite similar neuroendocrine responses among healthy adolescents and healthy adults, may reflect an interaction between developmental and depressed status.…”

Reason to Believe: Representations of Aggression as Phenomenological Read-Out

“…Whatever its manner of effect, studies indicate that a documented history of aggression (especially impulsive aggression), self-or clinician-ratings of aggressiveness, and laboratory measures of aggressive behavior are all associated with lower levels of serotonin in cerebrospinal fluid and in whole blood, reduced prolactin response to fenfluramine challenge, experimental depletion of dietary tryptophan (an amino acid needed for the synthesis of central 5-HT), and differences in the DNA sequence of the serotonin transporter gene (see reviews by Miczek, Weerts, Haney, & Tidey, 1994;Niehoff, 1999). Sex differences have been reported in serotonin uptake, especially in the frontal cortex responsible for behavioral inhibition (Biver et al, 1996;Bucht, Adolfsson, Gottfries, Roos, & Winblad, 1981;Heninger, Charney, & Sternberg, 1984;Maes et al, 1989;Odink, Korthals, & Vette, 1987;Reisert & Pilgrim, 1991).…”