METHODS: Female rats, once rendered hypothyroid via oral administration of methimazole (0.03% in drinking water) for twenty-one days were mated with fertile euthyroid male rats at 1:1 ratio. Pregnancy was confirmed by the presence of vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80 μg/kg/day) was then subcutaneously administered to pregnant, hypothyroid female rats for three days. A day after last injection (day four pregnancy), female rats were sacrificed and expression of thyroid hormone receptors (TR-α and β), retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in uterus were quantified by Western blotting while their distribution in endometrium was visualized by immunofluorescence.
RESULTS: Expression of TRα-1, TRβ-1 and ERK1/2 proteins in uterus increased with increasing doses of thyroxine however no changes in RXR expression was observed. These proteins were found in the stroma with their distribution levels were relatively higher following thyroxine treatment.
CONCLUSIONS: Increased expression of TRα-1, TRβ-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant rats indicate the importance of thyroxine in up-regulating expression of these proteins that could help mediate the uterine changes prior to embryo implantation.
Methods: Pseudopregnancy (pc) was induced in cyclic Sprague-Dawley rats by sterile mating. Subcutaneous injection of nicotine tartrate (7.5 mg/kg/day) was scheduled from day 1 through day 5, day 5 through day 9 or day 1 through day 9 of pc. In another group of pseudopregnant rats, concomitant treatment of nicotine tartrate concurrently with progesterone (2 mg/day) was scheduled from day 1 through day 9 pc. Control groups received subcutaneous injections of vehicle only. Endometrial decidualization was induced on day 5 pc. On day 10 pc, animals were sacrificed.The degree of decidual growth and circulating levels of estrogen and progesterone were measured.
Results: The decidual growth in all the first three nicotine-treated groups of animals was significantly reduced, particularly in the animals treated with nicotine from day 1 through day 9 pc. Plasma estrogen levels were significantly elevated in animals treated with nicotine from day 1 through day 9 pc. Conversely, levels of plasma progesterone were found to be significantly attenuated in the same group of nicotine-treated animals compared to controls. Exogenous replacement of progesterone, however, caused a higher degree of endometrial decidualization compared to the nicotine-treated group but it was slightly less than when compared to control.
Conclusions: In conclusion, nicotine-induced progesterone deficiency with a corresponding elevation of estrogen may possibly attenuate the degree of endometrial decidualization in pseudopregnant rats.
Objective: To investigate the acceptability and pharmacokinetics (PK) of SC injection of TU.
Design: Randomized sequence, crossover clinical study of SC vs IM TU injections.
Setting: Ambulatory clinic of an academic andrology center.
Participants: Twenty men (11 hypogonadal, 9 transgender men) who were long-term users of TU. injections. Intervention: Injection of 1000 mg TU (in 4 mL castor oil vehicle) by SC or IM route. Main Outcome Measures: Patient-reported pain, acceptability, and preference scales. PK by measurement of serum testosterone, dihydrotestosterone (DHT), and estradiol (E2) concentrations with application of population PK methods and dried blood spot (DBS) sampling.
Results: Pain was greater after SC compared with IM injection 24 hours (but not immediately) after injection but both routes were equally acceptable. Ultimately 11 preferred IM, 6 preferred SC, and 3 had no preference. The DBS-based PK analysis of serum testosterone revealed a later time of peak testosterone concentration after SC vs IM injection (8.0 vs 3.3 days) but no significant route differences in model-predicted peak testosterone concentration (8.4 vs 9.6 ng/mL) or mean resident time (183 vs 110 days). The PK of venous serum testosterone, DHT, and E2 did not differ according to route of injection.
Conclusions: We conclude that SC TU injection is acceptable but produces greater pain 24 hours after injection that may contribute to the overall majority preference for the IM injection. The PK of testosterone, DHT, or E2 did not differ substantially between SC and IM routes. Hence whereas further studies are required, the SC route represents an alternative to IM injections without a need to change dose for men for whom IM injection is not desired or recommended.